Literature for peptidase A22.001: presenilin 1

Summary Gene structure Alignment Tree Sequences Sequence features Distribution Structure Literature Substrates Pharma

(Topics flags: A Assay, S Structure, T Target, P Specificity, K Knockout, E Expression, V Review, M Mutation, R Splicing, I Inhibitor, L Localization. To select only the references relevant to a single topic, click the link above. See explanation.)

2025

Fremlen,H. and Burmann,B.M.
Maintaining the Integral Membrane Proteome: Revisiting the Functional Repertoire of Integral Membrane Proteases
Chembiocheme202500048-e202500048. PubMed Europe PubMed DOI V
Liu,H., Marsh,T.W., Shi,X., Renton,A.E., Bowling,K.M., Ziegemeier,E., Wang,G., Cao,Y., Aristel,A., Li,J., Dickson,A., Perrin,R.J., Goate,A.M., Fernandez,V., Day,G.S., Doering,M., Daniels,A., Gordon,B.A., Benzinger,T.L.S., Hassenstab,J., Ibanez,L., Supnet-Bell,C., Xiong,C., Allegri,R., Berman,S.B., Fox,N.C., Ryan,N., Huey,E.D., Voglein,J., Noble,J.M., Roh,J.H., Jucker,M., Laske,C., Ikeuchi,T., Sanchez-Valle,R., Schofield,P.R., Chrem Mendez,P., Chhatwal,J.P., Farlow,M., Lee,J.H., Levey,A.I., Levin,J., Lopera,F., Martins,R., Niimi,Y., Rosa-Neto,P., Morris,J.C., Bateman,R.J., Karch,C.M., Cruchaga,C., McDade,E. and Llibre-Guerra,J.J.
The landscape of autosomal-dominant Alzheimer's disease: global distribution and age of onset
Brain PubMed Europe PubMed DOI
Nadendla,S. and Mohiuddin,S.S.
Biochemistry, Presenilin
PubMed Europe PubMed

2024

Acosta-Uribe,J., Villegas-Lanau,A., Vallejo,D., Ramirez-Aguilar,L., Solano,J.M., Mejia-Cupajita,B., Aguillon,D., Moreno,S., Mendez,L.G., Baena,A., Madrigal,L., Bocanegra,Y., Quiroz,Y.T., Garcia,G.P., Vasquez,D., Arbelaez,A., Lopera,F., Beach,T.G., Kosik,K.S., White,C.L., III and Giraldo-Chica,M.
Primary lateral sclerosis associated with PSEN1 Pro284Leu variant in a Colombian family: Clinical and neuropathological features
Alzheimers Dement20, 6384-6394. PubMed Europe PubMed DOI
Arafi,P., Devkota,S., Maesako,M. and Wolfe,M.S.
Alzheimer-mutant gamma-secretase complexes stall amyloid beta-peptide production
bioRxiv PubMed Europe PubMed DOI
Colijn,M.A. and Ismail,Z.
Presenilin Gene Mutation-associated Psychosis: Phenotypic Characteristics and Clinical Implications
Alzheimer Dis Assoc Disord38, 101-106. PubMed Europe PubMed DOI V
Deng,C., Cai,Q., Zhang,J., Chang,K., Peng,T., Liu,X., Cao,F., Yan,X., Cheng,J., Wang,X., Tan,Y. and Hua,Q.
Generation and Characterization of a Novel Knockin Mouse Model Expressing PSEN1 D385A: Implications for Investigating Herbal Drug Effects in gamma-Secretase Activity
J Alzheimers Dis PubMed Europe PubMed DOI
Perrin,F., Anderson,L.C., Mitchell,S.P.C., Sinha,P., Turchyna,Y., Maesako,M., Houser,M.C.Q., Zhang,C., Wagner,S.L., Tanzi,R.E. and Berezovska,O.
PS1/gamma-secretase acts as rogue chaperone of glutamate transporter EAAT2/GLT-1 in Alzheimer's disease
Acta Neuropathol Commun12, 166-166. PubMed Europe PubMed DOI
Perrin,F., Sinha,P., Mitchell,S.P.C., Sadek,M., Maesako,M. and Berezovska,O.
Identification of PS1/gamma-secretase and glutamate transporter GLT-1 interaction sites
J Biol Chem300, 107172-107172. PubMed Europe PubMed DOI
Yan,K., Zhang,C., Kang,J., Montenegro,P. and Shen,J.
Cortical neurodegeneration caused by Psen1 mutations is independent of Abeta
Proc Natl Acad Sci U S A121, e2409343121-e2409343121. PubMed Europe PubMed DOI

2023

Avramouli,A., Krokidis,M.G., Exarchos,T.P. and Vlamos,P.
Protein Structure Prediction for Disease-Related Insertions/Deletions in Presenilin 1 Gene
Adv Exp Med Biol1423, 31-40. PubMed Europe PubMed DOI
Kurth,V., Ogorek,I., Munch,C., Lopez-Rios,J., Ousson,S., Lehmann,S., Nieweg,K., Roebroek,A.J.M., Pietrzik,C.U., Beher,D. and Weggen,S.
Pathogenic Abeta production by heterozygous PSEN1 mutations is intrinsic to the mutant protein and not mediated by conformational hindrance of wild-type PSEN1
J Biol Chem299, 104997-104997. PubMed Europe PubMed DOI
Makarov,M., Kushnireva,L., Papa,M. and Korkotian,E.
Presenilins and mitochondria-an intriguing link: mini-review
Front Neurosci17, 1249815-1249815. PubMed Europe PubMed DOI V
Schultz,S.A., Shirzadi,Z., Schultz,A.P., Liu,L., Fitzpatrick,C.D., McDade,E., Barthelemy,N.R., Renton,A., Esposito,B., Joseph-Mathurin,N., Cruchaga,C., Chen,C.D., Goate,A., Allegri,R.F., Benzinger,T.L.S., Berman,S., Chui,H.C., Fagan,A.M., Farlow,M.R., Fox,N.C., Gordon,B.A., Day,G.S., Graff-Radford,N.R., Hassenstab,J.J., Hanseeuw,B.J., Hofmann,A., Jack,C.R., Jr., Jucker,M., Karch,C.M., Koeppe,R.A., Lee,J.H., Levey,A.I., Levin,J., Martins,R.N., Mori,H., Morris,J.C., Noble,J., Perrin,R.J., Rosa-Neto,P., Salloway,S.P., Sanchez-Valle,R., Schofield,P.R., Xiong,C., Johnson,K.A., Bateman,R.J., Sperling,R.A. and Chhatwal,J.P.
Location of pathogenic variants in PSEN1 impacts progression of cognitive, clinical, and neurodegenerative measures in autosomal-dominant Alzheimer's disease
Aging Cell22, e13871-e13871. PubMed Europe PubMed DOI
Serneels,L., Narlawar,R., Perez-Benito,L., Municoy,M., Guallar,V., T'Syen,D., Dewilde,M., Bischoff,F., Fraiponts,E., Tresadern,G., Roevens,P.W.M., Gijsen,H.J.M. and De Strooper,B.
Selective inhibitors of the PSEN1-gamma-secretase complex
J Biol Chem299, 104794-104794. PubMed Europe PubMed DOI
Yang,Y., Bagyinszky,E. and An,S.S.A.
Presenilin-1 (PSEN1) Mutations: Clinical Phenotypes beyond Alzheimer's Disease
Int J Mol Sci24, PubMed Europe PubMed DOI

2022

Gamez-Belmonte,R., Mahapatro,M., Erkert,L., Gonzalez-Acera,M., Naschberger,E., Yu,Y., Tena-Garitaonaindia,M., Patankar,J.V., Wagner,Y., Podstawa,E., Schodel,L., Bubeck,M., Neurath,M.F., Sturzl,M. and Becker,C.
Epithelial presenilin-1 drives colorectal tumour growth by controlling EGFR-COX2 signalling
Gut PubMed Europe PubMed DOI
Zhu,W., Zhou,Y., Wang,Q., Li,J., Chu,S., Jin,W., Mao,C., Dong,L., Gao,J. and Xu,Q.
Generation of a human induced pluripotent stem cell (iPSC) line from skin fibroblasts of a patient carrying an E363Q mutation in PSEN1 gene
Stem Cell Res61, 102769-102769. PubMed Europe PubMed DOI

2021

Asada-Utsugi,M., Uemura,K., Kubota,M., Noda,Y., Tashiro,Y., Uemura,T.M., Yamakado,H., Urushitani,M., Takahashi,R., Hattori,S., Miyakawa,T., Ageta-Ishihara,N., Kobayashi,K., Kinoshita,M. and Kinoshita,A.
Mice with cleavage-resistant N-cadherin exhibit synapse anomaly in the hippocampus and outperformance in spatial learning tasks
Mol Brain14, 23-23. PubMed Europe PubMed DOI
Bustos,V., Pulina,M.V. and Ledo,J.
Amyloidogenic and anti-amyloidogenic properties of presenilin 1
Adv Pharmacol90, 239-251. PubMed Europe PubMed DOI
Cai,T. and Tomita,T.
Sequential conformational changes in transmembrane domains of presenilin 1 in Abeta42 downregulation
J Biochem PubMed Europe PubMed DOI
Joshi,P., Gardner,M., Lintott,C. and Anderson,T.
Novel Presenilin-1 Mutation (Ala275Ser) Associated With Clinical Features of Dementia With Lewy Bodies
Alzheimer Dis Assoc Disord PubMed Europe PubMed DOI V
Liu,L., Lauro,B.M., Wolfe,M.S. and Selkoe,D.J.
Hydrophilic loop 1 of Presenilin-1 and the APP GxxxG transmembrane motif regulate gamma-secretase function in generating Alzheimer-causing Abeta peptides
J Biol Chem100393-100393. PubMed Europe PubMed DOI
Yang,G., Zhou,R., Guo,X., Yan,C., Lei,J. and Shi,Y.
Structural basis of gamma-secretase inhibition and modulation by small molecule drugs
Cell184, 521-533. PubMed Europe PubMed DOI I

2020

Barman,N.C., Khan,N.M., Islam,M., Nain,Z., Roy,R.K., Haque,A. and Barman,S.K.
CRISPR-Cas9: A Promising Genome Editing Therapeutic Tool for Alzheimer's Disease-A Narrative Review
Neurol Ther9, 419-434. PubMed Europe PubMed DOI V
Cai,T. and Tomita,T.
Structure-activity relationship of presenilin in gamma-secretase-mediated intramembrane cleavage
Semin Cell Dev Biol PubMed Europe PubMed DOI
Cai,T., Hatano,A., Kanatsu,K. and Tomita,T.
Histidine 131 in presenilin 1 is the pH-sensitive residue that causes the increase in Abeta42 level in acidic pH
J Biochem167, 463-471. PubMed Europe PubMed DOI
Contino,S., Suelves,N., Vrancx,C., Vadukul,D.M., Payen,V.L., Stanga,S., Bertrand,L. and Kienlen-Campard,P.
Presenilin-Deficient Neurons and Astrocytes Display Normal Mitochondrial Phenotypes
Front Neurosci14, 586108-586108. PubMed Europe PubMed DOI K
Dehury,B., Somavarapu,A.K. and Kepp,K.P.
A computer-simulated mechanism of familial Alzheimer's disease: Mutations enhance thermal dynamics and favor looser substrate-binding to gamma-secretase
J Struct Biol212, 107648-107648. PubMed Europe PubMed DOI
Escamilla-Ayala,A., Wouters,R., Sannerud,R. and Annaert,W.
Contribution of the presenilins in the cell biology, structure and function of gamma-secretase
Semin Cell Dev Biol PubMed Europe PubMed DOI
Escamilla-Ayala,A.A., Sannerud,R., Mondin,M., Poersch,K., Vermeire,W., Paparelli,L., Berlage,C., Koenig,M., Chavez-Gutierrez,L., Ulbrich,M.H., Munck,S., Mizuno,H. and Annaert,W.
Super-resolution microscopy reveals majorly mono- and dimeric presenilin1/gamma-secretase at the cell surface
elife9, PubMed Europe PubMed DOI
Fan,C., Huang,X., Song,H. and Jia,J.
Presenilin 1 intronic polymorphism in sporadic Alzheimer's disease in a Northern Chinese population
Neuroreport31, 37-40. PubMed Europe PubMed DOI M
Fray,S., Rassas,A., Messaoud,T. and Belal,S.
Refractory epilepsy in PSEN 1 mutation (I83T)
Neurocase26, 167-170. PubMed Europe PubMed DOI M
Gu,X., Zhao,M., Han,X. and Liu,L.
Presenilin-1 mutation is associated with a hippocampus defect in Alzheimer's disease: meta-analysis for neuroimaging research
Clin Neurol Neurosurg191, 105679-105679. PubMed Europe PubMed DOI M
Jiang,H., Pederson,S.M., Newman,M., Dong,Y., Barthelson,K. and Lardelli,M.
Transcriptome analysis indicates dominant effects on ribosome and mitochondrial function of a premature termination codon mutation in the zebrafish gene psen2
PLoS ONE15, e0232559-e0232559. PubMed Europe PubMed DOI
Kabir,M.T., Uddin,M.S., Setu,J.R., Ashraf,G.M., Bin-Jumah,M.N. and Abdel-Daim,M.M.
Exploring the Role of PSEN Mutations in the Pathogenesis of Alzheimer's Disease
Neurotox Res PubMed Europe PubMed DOI
Mehra,R. and Kepp,K.P.
Identification of structural calcium binding sites in membrane-bound presenilin 1 and 2
J Phys Chem B PubMed Europe PubMed DOI
Mengel,D., Liu,L., Yamamoto,R., Zulow,S., Deuschl,C., Hermann,D.M., Zerr,I., Selkoe,D.J. and Dodel,R.
A novel V272D presenilin mutation associated with logopenia, disorientation, and apraxia in an autosomal-dominant Alzheimer's disease family
Neurobiol Aging85, e5-e154. PubMed Europe PubMed DOI M
Norton,D.J., Parra,M.A., Sperling,R.A., Baena,A., Guzman-Velez,E., Jin,D.S., Andrea,N., Khang,J., Schultz,A., Rentz,D.M., Pardilla-Delgado,E., Fuller,J., Johnson,K., Reiman,E.M., Lopera,F. and Quiroz,Y.T.
Visual short-term memory relates to tau and amyloid burdens in preclinical autosomal dominant Alzheimer's disease
Alzheimers Res Ther12, 99-99. PubMed Europe PubMed DOI
Oakley,D.H., Chung,M., Klickstein,N., Commins,C., Hyman,B.T. and Frosch,M.P.
The Alzheimer disease-causing presenilin-1 L435F mutation causes increased production of soluble Abeta43 species in patient-derived iPSC-neurons, closely mimicking matched patient brain tissue
J Neuropathol Exp Neurol79, 592-604. PubMed Europe PubMed DOI M
Piaceri,I., Chiari,A., Galli,C., Bagnoli,S., Ferrari,C., Saavedra,S.T., Molinari,M.A., Vinceti,G., Sorbi,S. and Nacmias,B.
Incomplete penetrance in familial Alzheimer's disease with PSEN1 Ala260Gly mutation
Neurol Sci PubMed Europe PubMed DOI M
Pimenova,A.A. and Goate,A.M.
Novel presenilin 1 and 2 double knock-out cell line for in vitro validation of PSEN1 and PSEN2 mutations
Neurobiol Dis138, 104785-104785. PubMed Europe PubMed DOI K
Qiu,Q., Jia,L., Wang,Q., Zhao,L., Jin,H., Li,T., Quan,M., Xu,L., Li,B., Li,Y. and Jia,J.
Identification of a novel PSEN1 Gly111Val missense mutation in a Chinese pedigree with early-onset Alzheimer's disease
Neurobiol Aging85, e1-e155. PubMed Europe PubMed DOI M
Santos-Mandujano,R.A., Ryan,N.S., Chavez-Gutierrez,L., Sanchez-Torres,C. and Meraz-Rios,M.A.
Clinical association of white matter hyperintensities localization in a Mexican family with spastic paraparesis carrying the PSEN1 A431E mutation
J Alzheimers Dis73, 1075-1083. PubMed Europe PubMed DOI M
Schrank,S., McDaid,J., Briggs,C.A., Mustaly-Kalimi,S., Brinks,D., Houcek,A., Singer,O., Bottero,V., Marr,R.A. and Stutzmann,G.E.
Human-induced neurons from presenilin 1 mutant patients model aspects of Alzheimer's disease pathology
Int J Mol Sci21, PubMed Europe PubMed DOI M
Soto-Mercado,V., Mendivil-Perez,M., Velez-Pardo,C., Lopera,F. and Jimenez-Del-Rio,M.
Cholinergic-like neurons carrying PSEN1 E280A mutation from familial Alzheimer's disease reveal intraneuronal sAPPbeta fragments accumulation, hyperphosphorylation of TAU, oxidative stress, apoptosis and Ca2+ dysregulation: therapeutic implications
PLoS ONE15, e0221669-e0221669. PubMed Europe PubMed DOI M
Wang,C.Y., Zhang,Q., Xun,Z., Yuan,L., Li,R., Li,X., Tian,S.Y., Xin,N. and Xu,Y.
Increases of iASPP-Keap1 interaction mediated by syringin enhance synaptic plasticity and rescue cognitive impairments via stabilizing Nrf2 in Alzheimer's models
Redox Biol36, 101672-101672. PubMed Europe PubMed DOI
Wang,Y., Yang,J.Q., Hong,T.T., Sun,Y.H., Huang,H.L., Chen,F., Chen,X.J., Chen,H.Y., Dong,S.S., Cui,L.L. and Yang,T.L.
RTN4B-mediated suppression of Sirtuin 2 activity ameliorates beta-amyloid pathology and cognitive impairment in Alzheimer's disease mouse model
Aging Celle13194-e13194. PubMed Europe PubMed DOI
Wong,T.H., Seelaar,H., Melhem,S., Rozemuller,A.J.M. and van Swieten,J.C.
Genetic screening in early-onset Alzheimer's disease identified three novel presenilin mutations
Neurobiol Aging86, e9-e201. PubMed Europe PubMed DOI M
You,C., Zeng,W., Deng,L., Lei,Z., Gao,X., Zhang,V.W. and Wang,Y.
Identification and clinical analysis of the first nonsense mutation in the PSEN1 gene in a family with acute encephalopathy and retinitis pigmentosa
Front Neurol11, 319-319. PubMed Europe PubMed DOI M

2019

Selective gamma-secretase inhibition is a potential target for leukemias
Cancer Discov9, OF15-OF15. PubMed Europe PubMed DOI I
Aathi,M. and Piramanayagam,S.
From EST to structure models for functional inference of APP, BACE1, PSEN1, PSEN2 genes
Bioinformation15, 760-771. PubMed Europe PubMed DOI I
Arber,C., Villegas-Llerena,C., Toombs,J., Pocock,J.M., Ryan,N.S., Fox,N.C., Zetterberg,H., Hardy,J. and Wray,S.
Amyloid precursor protein processing in human neurons with an allelic series of the PSEN1 intron 4 deletion mutation and total presenilin-1 knockout
Brain Commun1, fcz024-fcz024. PubMed Europe PubMed DOI M
Artuso,V., Benussi,L., Ghidoni,R., Moradi-Bachiller,S., Fusco,F., Curtolo,S., Roiter,I., Forloni,G. and Albani,D.
Asymptomatic carriers of presenilin-1 E318G variant show no cerebrospinal fluid biochemical signs suggestive of Alzheimer's disease in a family with late-onset dementia
Curr Alzheimer Res16, 1-7. PubMed Europe PubMed DOI M
Auboyer,L., Monzo,C., Wallon,D., Rovelet-Lecrux,A., Gabelle,A., Gazagne,I., Cacheux,V., Lehmann,S. and Crozet,C.
Generation of induced pluripotent stem cells (IRMBi001-A) from an Alzheimer's disease patient carrying a G217D mutation in the PSEN1 gene
Stem Cell Res34, 101381-101381. PubMed Europe PubMed DOI M
Blanco,J.A., Alonso,A., Blanco,J., Rojo,E., Telleria,J.J., Torres,M.A. and Uribe,F.
Novel presenilin 1 mutation (p.Thr-Pro116-117Ser-Thr) in a Spanish family with early-onset Alzheimer's disease
Neurobiol Aging84, e19-e238. PubMed Europe PubMed DOI M
Cai,T., Morishima,K., Takagi-Niidome,S., Tominaga,A. and Tomita,T.
Conformational dynamics of transmembrane domain 3 of presenilin 1 is associated with the trimming activity of gamma-secretase
J Neurosci39, 8600-8610. PubMed Europe PubMed DOI
Chavez-Garcia,C., Aguayo-Ortiz,R. and Dominguez,L.
Quantifying correlations between mutational sites in the catalytic subunit of gamma-secretase
J Mol Graph Model88, 221-227. PubMed Europe PubMed DOI M
Cho,Y.Y., Kwon,O.H., Park,M.K., Kim,T.W. and Chung,S.
Elevated cellular cholesterol in familial Alzheimer's presenilin 1 mutation is associated with lipid raft localization of beta-amyloid precursor protein
PLoS ONE14, e0210535-e0210535. PubMed Europe PubMed DOI M
Diaz-Guerra,E., Oria-Muriel,M.A., Moreno-Jimenez,E.P., de Rojasb,I., Rodriguez,C., Rodriguez-Traver,E., Orera,M., Hernandezb,I., Ruizb,A. and Vicario,C.
Generation of an integration-free iPSC line, ICCSICi006-A, derived from a male Alzheimer's disease patient carrying the PSEN1-G206D mutation
Stem Cell Res40, 101574-101574. PubMed Europe PubMed DOI M
Gao,Y., Ren,R.J., Zhong,Z.L., Dammer,E., Zhao,Q.H., Shan,S., Zhou,Z., Li,X., Zhang,Y.Q., Cui,H.L., Hu,Y.B., Chen,S.D., Chen,J.J., Guo,Q.H. and Wang,G.
Mutation profile of APP, PSEN1, and PSEN2 in Chinese familial Alzheimer's disease
Neurobiol Aging77, 154-157. PubMed Europe PubMed DOI M
Giau,V.V., Bagyinszky,E., Yang,Y.S., Youn,Y.C., An,S.S.A. and Kim,S.Y.
Genetic analyses of early-onset Alzheimer's disease using next generation sequencing
Sci Rep9, 8368-8368. PubMed Europe PubMed DOI M
Guven,G., Erginel-Unaltuna,N., Samanci,B., Gulec,C., Hanagasi,H. and Bilgic,B.
A patient with early-onset Alzheimer's disease with a novel PSEN1 p.Leu424Pro mutation
Neurobiol Aging84, e1-e238. PubMed Europe PubMed DOI M
Hitzenberger,M. and Zacharias,M.
Structural modeling of gamma-secretase Abetan complex formation and substrate processing
ACS Chem Neurosci10, 1826-1840. PubMed Europe PubMed DOI
Imai,S., Cai,T., Yoshida,C., Tomita,T. and Futai,E.
Specific mutations in presenilin 1 cause conformational changes in gamma-secretase to modulate amyloid beta trimming
J Biochem165, 37-46. PubMed Europe PubMed DOI M
Jo,H., Kim,M., Park,S., Park,J.E., Cho,S.H., Kim,S.J., Jang,H., Jung,Y.H., Kim,J., Na,D.L., Seo,S.W., Cho,J.W. and Kim,H.J.
Dopa responsive Parkinsonism in an early onset Alzheimer's disease patient with a presenilin 1 mutation (A434T)
J Alzheimers Dis71, 7-13. PubMed Europe PubMed DOI M
Kounnas,M.Z., Durakoglugil,M.S., Herz,J. and Comer,W.T.
NGP 555, a gamma-secretase modulator, shows a beneficial shift in the ratio of amyloid biomarkers in human cerebrospinal fluid at safe doses
Alzheimers Dement (N Y)5, 458-467. PubMed Europe PubMed DOI
Li,Y.S., Yang,Z.H., Zhang,Y., Yang,J., Shang,D.D., Zhang,S.Y., Wu,J., Ji,Y., Zhao,L., Shi,C.H. and Xu,Y.M.
Two novel mutations and a de novo mutation in PSEN1 in early-onset Alzheimer's disease
Aging Dis10, 908-914. PubMed Europe PubMed DOI M
Liu,L., Ding,L., Rovere,M., Wolfe,M.S. and Selkoe,D.J.
A cellular complex of BACE1 and gamma-secretase sequentially generates Abeta from its full-length precursor
J Cell Biol218, 644-663. PubMed Europe PubMed DOI
Lopez-Garcia,S., Jimenez-Bonilla,J., Lopez Delgado,A., Orizaola Balaguer,P., Infante Ceberio,J., Banzo Marraco,I., Rodriguez Rodriguez,E. and Sanchez-Juan,P.
A rare PSEN1 (Leu85Pro) mutation causing Alzheimer's disease in a 29-year-old woman presenting as corticobasal syndrome
J Alzheimers Dis70, 655-658. PubMed Europe PubMed DOI M
Miki,T., Yokota,O., Haraguchi,T., Ikeuchi,T., Zhu,B., Takenoshita,S., Terada,S. and Yamada,N.
Young adult-onset, very slowly progressive cognitive decline with spastic paraparesis in Alzheimer's disease with cotton wool plaques due to a novel presenilin1 G417S mutation
Acta Neuropathol Commun7, 19-19. PubMed Europe PubMed DOI M
Monacelli,F., Martella,L., Parodi,M.N., Odetti,P., Fanelli,F. and Tabaton,M.
Frontal variant of Alzheimer's disease: a report of a novel PSEN1 mutation
J Alzheimers Dis70, 11-15. PubMed Europe PubMed DOI M
Newman,M., Hin,N., Pederson,S. and Lardelli,M.
Brain transcriptome analysis of a familial Alzheimer's disease-like mutation in the zebrafish presenilin 1 gene implies effects on energy production
Mol Brain12, 43-43. PubMed Europe PubMed DOI K M
Oikawa,N. and Walter,J.
Presenilins and gamma-secretase in membrane proteostasis
Cells8, PubMed Europe PubMed DOI
Qiu,Q., Shen,L., Jia,L., Wang,Q., Li,F., Li,Y. and Jia,J.
A novel PSEN1 M139L mutation found in a Chinese pedigree with early-onset Alzheimer's disease increases Abeta42/Abeta40 ratio
J Alzheimers Dis69, 199-212. PubMed Europe PubMed DOI M
Ramirez Aguilar,L., Acosta-Uribe,J., Giraldo,M.M., Moreno,S., Baena,A., Alzate,D., Cuastumal,R., Aguillon,D., Madrigal,L., Saldarriaga,A., Navarro,A., Garcia,G.P., Aguirre-Acevedo,D.C., Geier,E.G., Cochran,J.N., Quiroz,Y.T., Myers,R.M., Yokoyama,J.S., Kosik,K.S. and Lopera,F.
Genetic origin of a large family with a novel PSEN1 mutation (Ile416Thr)
Alzheimers Dement15, 709-719. PubMed Europe PubMed DOI M
Shen,L., Qin,W., Wu,L., Zhou,A., Tang,Y., Wang,Q., Jia,L. and Jia,J.
Two novel presenilin-1 mutations (I249L and P433S) in early onset Chinese Alzheimer's pedigrees and their functional characterization
Biochem Biophys Res Commun516, 264-269. PubMed Europe PubMed DOI M
Tang,N., Dehury,B. and Kepp,K.P.
Computing the pathogenicity of Alzheimer's disease presenilin 1 mutations
J Chem Inf Model59, 858-870. PubMed Europe PubMed DOI M
Vallejo-Diez,S., Fleischer,A., Martin-Fernandez,J.M., Sanchez-Gilabert,A., Castresana,M., Aguillon,D., Villegas,A., Mastronardi,C.A., Espinosa,L.G., Arcos-Burgos,M., Del Pozo,A., Herran,E., Gainza,E., Isaza-Ruget,M., Lopera,F. and Bachiller,D.
Generation of one iPSC line (IMEDEAi006-A) from an early-onset familial Alzheimer's Disease (fAD) patient carrying the E280A mutation in the PSEN1 gene
Stem Cell Res37, 101440-101440. PubMed Europe PubMed DOI M
Van Giau,V., Pyun,J.M., Suh,J., Bagyinszky,E., An,S.S.A. and Kim,S.Y.
A pathogenic PSEN1 Trp165Cys mutation associated with early-onset Alzheimer's disease
BMC Neurol19, 188-188. PubMed Europe PubMed DOI M
Villalba,A.C., Garcia,J., Ramos,C., Cuastumal,A.R., Aguillon,D., Aguirre-Acevedo,D.C., Madrigal,L. and Lopera,F.
Mental disorders in young adults from families with the presenilin-1 gene mutation E280A in the preclinical stage of Alzheimer's disease
J Alzheimers Dis PubMed Europe PubMed DOI M
Voglein,J., Willem,M., Trambauer,J., Schonecker,S., Dieterich,M., Biskup,S., Giudici,C., Utz,K., Oberstein,T., Brendel,M., Rominger,A., Danek,A., Steiner,H., Haass,C. and Levin,J.
Identification of a rare presenilin 1 single amino acid deletion mutation (F175del) with unusual amyloid-beta processing effects
Neurobiol Aging84, e5-e241. PubMed Europe PubMed DOI M
Wang,H., Sun,R., Shi,Y., Xia,M., Zhao,J., Yang,M., Ma,L., Sun,Y., Li,G., Zhang,H., Qin,W. and Zhang,J.
Probable novel PSEN1 Gln222Leu mutation in a Chinese family with early-onset Alzheimer's disease
Curr Alzheimer Res16, 764-769. PubMed Europe PubMed DOI M
Wolfe,M.S.
Dysfunctional gamma-Secretase in Familial Alzheimer's Disease
Neurochem Res44, 5-11. PubMed Europe PubMed DOI M
Wu,S., Song,W., Wong,C.C.L. and Shi,Y.
Bax inhibitor 1 is a gamma-secretase-independent presenilin-binding protein
Proc Natl Acad Sci U S A116, 141-147. PubMed Europe PubMed DOI M
Yang,G., Zhou,R., Zhou,Q., Guo,X., Yan,C., Ke,M., Lei,J. and Shi,Y.
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2018

Aguayo-Ortiz,R. and Dominguez,L.
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Barthet,G., Jorda-Siquier,T., Rumi-Masante,J., Bernadou,F., Muller,U. and Mulle,C.
Presenilin-mediated cleavage of APP regulates synaptotagmin-7 and presynaptic plasticity
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Adult hippocampal neurogenesis occurs in the absence of presenilin 1 and presenilin 2
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Giau,V.V., Wang,M.J., Bagyinszky,E., Youn,Y.C., An,S.S.A. and Kim,S.
Novel PSEN1 p.Gly417Ala mutation in a Korean patient with early-onset Alzheimer's disease with parkinsonism
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Hsu,S., Gordon,B.A., Hornbeck,R., Norton,J.B., Levitch,D., Louden,A., Ziegemeier,E., Laforce R Jr, Chhatwal,J., Day,G.S., McDade,E., Morris,J.C., Fagan,A.M., Benzinger,T.L.S., Goate,A.M., Cruchaga,C., Bateman,R.J. and Karch,C.M.
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Huang,Q., Voloudakis,G., Ren,Y., Yoon,Y., Zhang,E., Kajiwara,Y., Shao,Z., Xuan,Z., Lebedev,D., Georgakopoulos,A. and Robakis,N.K.
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Khan,I., Krishnaswamy,S., Sabale,M., Groth,D., Wijaya,L., Morici,M., Berger,I., Schaffitzel,C., Fraser,P.E., Martins,R.N. and Verdile,G.
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Liu,Z., Thakar,A., Santoro,S.W. and Pratt,K.G.
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Shi,T.W., Bai,N., Zhang,J.A., Lu,F., Chen,X.B., Kong,X.D. and Yu,J.B.
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Stanga,S., Vrancx,C., Tasiaux,B., Marinangeli,C., Karlstrom,H. and Kienlen-Campard,P.
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J Cell Mol Med22, 823-833. PubMed Europe PubMed DOI I
Stenovec,M., Trkov Bobnar,S., Smolic,T., Kreft,M., Parpura,V. and Zorec,R.
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A novel presenilin 1 mutation (Leu418Trp) associated with spasticity, parkinsonism, and white matter lesion in a dominant Alzheimer's family
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2017

Aguayo-Ortiz,R., Chavez-Garcia,C., Straub,J.E. and Dominguez,L.
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Design, synthesis and evaluation of a novel series of oxadiazine gamma secretase modulators for familial Alzheimer's disease
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Dong,J., Qin,W., Wei,C., Tang,Y., Wang,Q. and Jia,J.
A novel PSEN1 K311R mutation discovered in Chinese families with late-onset Alzheimer's disease affects amyloid-beta production and tau phosphorylation
J Alzheimers Dis57, 613-623. PubMed Europe PubMed DOI M
Frost,G.R., Wong,E. and Li,Y.M.
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The novel PSEN1 M84V mutation associated to frontal dysexecutive syndrome, spastic paraparesis, and cerebellar atrophy in a dominant Alzheimer's disease family
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Gertsik,N., Am Ende,C.W., Geoghegan,K.F., Nguyen,C., Mukherjee,P., Mente,S., Seneviratne,U., Johnson,D.S. and Li,Y.M.
Mapping the binding site of BMS-708163 on gamma-secretase with cleavable photoprobes
Cell Chem Biol24, 3-8. PubMed Europe PubMed DOI I
Grigorenko,A.P., Moliaka,Y.K., Plotnikova,O.V., Smirnov,A., Nikishina,V.A., Goltsov,A.Y., Gusev,F., Andreeva,T.V., Nelson,O., Bezprozvanny,I. and Rogaev,E.I.
Mutational re-modeling of di-aspartyl intramembrane proteases: uncoupling physiologically-relevant activities from those associated with Alzheimer's disease
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Hu,C., Xu,J., Zeng,L., Li,T., Cui,M.Z. and Xu,X.
Pen-2 and presenilin are sufficient to catalyze notch processing
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Johnson,D.S., Li,Y.M., Pettersson,M. and St George-Hyslop,P.H.
Structural and chemical biology of presenilin complexes
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An evolutionarily conserved role of presenilin in neuronal protection in the aging Drosophila brain
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APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases
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Lee,J.Y., Feng,Z., Xie,X.Q. and Bahar,I.
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Two novel mutations in the first transmembrane domain of presenilin1 cause young-onset Alzheimer's disease
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Maesako,M., Horlacher,J., Zoltowska,K.M., Kastanenka,K.V., Kara,E., Svirsky,S., Keller,L.J., Li,X., Hyman,B.T., Bacskai,B.J. and Berezovska,O.
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Martin-Maestro,P., Gargini,R., A Sproul,A., Garcia,E., Anton,L.C., Noggle,S., Arancio,O., Avila,J. and Garcia-Escudero,V.
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Natelson Love,M., Clark,D.G., Cochran,J.N., Den Beste,K.A., Geldmacher,D.S., Benzinger,T.L., Gordon,B.A., Morris,J.C., Bateman,R.J. and Roberson,E.D.
Clinical, imaging, pathological, and biochemical characterization of a novel presenilin 1 mutation (N135Y) causing Alzheimer's disease
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Park,J., An,S.S.A., Giau,V.V., Shim,K., Youn,Y.C., Bagyinszky,E. and Kim,S.
Identification of a novel PSEN1 mutation (Leu232Pro) in a Korean patient with early-onset Alzheimer's disease and a family history of dementia
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Sun,L., Zhou,R., Yang,G. and Shi,Y.
Analysis of 138 pathogenic mutations in presenilin-1 on the in vitro production of Abeta42 and Abeta40 peptides by gamma-secretase
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Szaruga,M., Munteanu,B., Lismont,S., Veugelen,S., Horre,K., Mercken,M., Saido,T.C., Ryan,N.S., De Vos,T., Savvides,S.N., Gallardo,R., Schymkowitz,J., Rousseau,F., Fox,N.C., Hopf,C., De Strooper,B. and Chavez-Gutierrez,L.
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Semagacestat is a pseudo-inhibitor of gamma-secretase
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Probing the structure and function relationships of presenilin by substituted-cysteine accessibility method
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Defining the minimum substrate and charge recognition model of gamma-secretase
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Zhou,R., Yang,G. and Shi,Y.
Dominant negative effect of the loss-of-function gamma-secretase mutants on the wild-type enzyme through heterooligomerization
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2016

An,S.S., Bagyinszky,E., Kim,H.R., Seok,J.W., Shin,H.W., Bae,S., Kim,S. and Youn,Y.C.
Novel PSEN1 G209A mutation in early-onset Alzheimer dementia supported by structural prediction
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Blain,J.F., Bursavich,M.G., Freeman,E.A., Hrdlicka,L.A., Hodgdon,H.E., Chen,T., Costa,D.E., Harrison,B.A., Kapadnis,S., Murphy,D.A., Nolan,S., Tu,Z., Tang,C., Burnett,D.A., Patzke,H. and Koenig,G.
Characterization of FRM-36143 as a new gamma-secretase modulator for the potential treatment of familial Alzheimer's disease
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Bolduc,D.M., Montagna,D.R., Seghers,M.C., Wolfe,M.S. and Selkoe,D.J.
The amyloid-beta forming tripeptide cleavage mechanism of gamma-secretase
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Bolduc,D.M., Montagna,D.R., Gu,Y., Selkoe,D.J. and Wolfe,M.S.
Nicastrin functions to sterically hinder gamma-secretase-substrate interactions driven by substrate transmembrane domain
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Chavez-Gutierrez,L. and De Strooper,B.
Probing gamma-secretase-substrate interactions at the single amino acid residue level
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Crump,C.J., Murrey,H.E., Ballard,T.E., Am Ende,C.W., Wu,X., Gertsik,N., Johnson,D.S. and Li,Y.M.
Development of sulfonamide photoaffinity inhibitors for probing cellular gamma-secretase
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Beyond gamma-secretase activity: the multifunctional nature of presenilins in cell signalling pathways
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Fray,S., Ali,N.B., Rassas,A.A., Kechaou,M., Oudiaa,N., Cherif,A., Echebbi,S., Messaoud,T. and Belal,S.
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Hu,C., Zeng,L., Li,T., Meyer,M.A., Cui,M.Z. and Xu,X.
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Kretner,B., Trambauer,J., Fukumori,A., Mielke,J., Kuhn,P.H., Kremmer,E., Giese,A., Lichtenthaler,S.F., Haass,C., Arzberger,T. and Steiner,H.
Generation and deposition of Abeta43 by the virtually inactive presenilin-1 L435F mutant contradicts the presenilin loss-of-function hypothesis of Alzheimer's disease
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Li,N., Liu,K., Qiu,Y., Ren,Z., Dai,R., Deng,Y. and Qing,H.
Effect of presenilin mutations on APP cleavage; insights into the pathogenesis of FAD
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Meckler,X. and Checler,F.
Presenilin 1 and presenilin 2 target gamma-secretase complexes to distinct cellular compartments
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Molecular insight of DREAM and presenilin 1 C-terminal fragment interactions
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Novel PSEN1 mutations (H214N and R220P) associated with familial Alzheimer's disease identified by targeted exome sequencing
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Poon,A., Li,T., Pires,C., Nielsen,T.T., Nielsen,J.E., Holst,B., Dinnyes,A., Hyttel,P. and Freude,K.K.
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Poon,A., Schmid,B., Pires,C., Nielsen,T.T., Hjermind,L.E., Nielsen,J.E., Holst,B., Hyttel,P. and Freude,K.K.
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Scannevin,R.H., Chollate,S., Brennan,M.S., Snodgrass-Belt,P.A., Peng,H., Xu,L., Jung,M.Y., Bussiere,T., Arastu,M.F., Talreja,T., Xin,Z., Dunstan,R.W., Fahrer,D., Rohde,E., Dunah,A.W., Wang,J., Kumaravel,G., Taveras,A.G., Moore Arnold,H. and Rhodes,K.J.
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The dynamic mechanism of presenilin-1 function: sensitive gate dynamics and loop unplugging control protein access
Neurobiol Dis89, 147-156. PubMed Europe PubMed DOI
Somavarapu,A.K. and Kepp,K.P.
Loss of stability and hydrophobicity of presenilin 1 mutations causing Alzheimer's Disease
J Neurochem137, 101-111. PubMed Europe PubMed DOI M
Tedde,A., Bartoli,A., Piaceri,I., Ferrara,S., Bagnoli,S., Serio,A., Sorbi,S. and Nacmias,B.
Novel presenilin 1 mutation (Ile408Thr) in an Italian family with late-onset Alzheimer's disease
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Theobald,D.L.
Presenilin adopts the ClC channel fold
Protein Sci25, 1363-1365. PubMed Europe PubMed DOI S
Tominaga,A., Cai,T., Takagi-Niidome,S., Iwatsubo,T. and Tomita,T.
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Tong,B.C., Lee,C.S., Cheng,W.H., Lai,K.O., Foskett,J.K. and Cheung,K.H.
Familial Alzheimer's disease-associated presenilin 1 mutants promote gamma-secretase cleavage of STIM1 to impair store-operated Ca2+ entry
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Toyn,J.H., Boy,K.M., Raybon,J., Meredith,J.E., Robertson,A.S., Guss,V., Hoque,N., Sweeney,F., Zhuo,X., Clarke,W., Snow,K., Denton,R.R., Zuev,D., Thompson,L.A., Morrison,J., Grace,J., Berisha,F., Furlong,M., Wang,J.-S., Lentz,K.A., Padmanabha,R., Cook,L., Wei,C., Drexler,D.M., Macor,J.E., Albright,C.F., Gasior,M., Olson,R.E., Hong,Q., Soares,H.D., AbuTarif,M. and Ahlijanian,M.K.
Robust translation of gamma-secretase modulator pharmacology across preclinical species and human subjects
J Pharmacol Exp Ther358, 125-137. PubMed Europe PubMed DOI
Veugelen,S., Saito,T., Saido,T.C., Chavez-Gutierrez,L. and De Strooper,B.
Familial Alzheimer's disease mutations in presenilin generate amyloidogenic Abeta peptide seeds
Neuron90, 410-416. PubMed Europe PubMed DOI M
Wu,W.L., Burnett,D.A., Clader,J., Greenlee,W.J., Jiang,Q., Hyde,L.A., Del Vecchio,R.A., Cohen-Williams,M.E., Song,L., Lee,J., Terracina,G., Zhang,Q., Nomeir,A., Parker,E.M. and Zhang,L.
Design and synthesis of water soluble beta-aminosulfone analogues of SCH 900229 as gamma-secretase inhibitors
Bioorg Med Chem Lett26, 5836-5841. PubMed Europe PubMed DOI I
Yonemura,Y., Futai,E., Yagishita,S., Kaether,C. and Ishiura,S.
Specific combinations of presenilins and Aph1s affect the substrate specificity and activity of gamma-secretase
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Zhao,Z., Pissarnitski,D.A., Josien,H.B., Bara,T.A., Clader,J.W., Li,H., McBriar,M.D., Rajagopalan,M., Xu,R., Terracina,G., Hyde,L., Song,L., Zhang,L., Parker,E.M., Osterman,R. and Buevich,A.V.
Substituted 4-morpholine N-arylsulfonamides as gamma-secretase inhibitors
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2015

Achouri-Rassas,A., BenAli,N., Fray,S., HadjFredj,S., Kechaou,M., Zakraoui,N.O., Cherif,A., Chabbi,S., Anane,N., Messaoud,T., Gouider,R. and Belal,S.
Novel presenilin 1 mutation (p.I83T) in Tunisian family with early-onset Alzheimer's disease
Neurobiol Aging36, e9-e11. PubMed Europe PubMed DOI M
Araki,W. and Tamaoka,A.
Amyloid beta-protein and lipid rafts: focused on biogenesis and catabolism
Front Biosci (Landmark Ed)20, 314-324. PubMed Europe PubMed DOI V
Bai,X.C., Yan,C., Yang,G., Lu,P., Ma,D., Sun,L., Zhou,R., Scheres,S.H. and Shi,Y.
An atomic structure of human gamma-secretase
Nature525, 212-217. PubMed Europe PubMed DOI S
Bai,X.C., Rajendra,E., Yang,G., Shi,Y. and Scheres,S.H.
Sampling the conformational space of the catalytic subunit of human gamma-secretase
elife4, PubMed Europe PubMed DOI S I
Bonds,J.A., Kuttner-Hirshler,Y., Bartolotti,N., Tobin,M.K., Pizzi,M., Marr,R. and Lazarov,O.
Presenilin-1 dependent neurogenesis regulates hippocampal learning and memory
PLoS ONE10, e0131266-e0131266. PubMed Europe PubMed DOI
Brautigam,H., Moreno,C.L., Steele,J.W., Bogush,A., Dickstein,D.L., Kwok,J.B., Schofield,P.R., Thinakaran,G., Mathews,P.M., Hof,P.R., Gandy,S. and Ehrlich,M.E.
Physiologically generated presenilin 1 lacking exon 8 fails to rescue brain PS1-/- phenotype and forms complexes with wildtype PS1 and nicastrin
Sci Rep5, 17042-17042. PubMed Europe PubMed DOI M
Chen,W.T., Hsieh,Y.F., Huang,Y.J., Lin,C.C., Lin,Y.T., Liu,Y.C., Lien,C.C. and Cheng,I.H.
G206D Mutation of presenilin-1 reduces Pen2 interaction, increases Abeta42/Abeta40 ratio and elevates ER Ca(2+) accumulation
Mol Neurobiol52, 1835-1849. PubMed Europe PubMed DOI M
Chu,J., Li,J.G., Joshi,Y.B., Giannopoulos,P.F., Hoffman,N.E., Madesh,M. and Pratico,D.
Gamma secretase-activating protein is a substrate for caspase-3: implications for Alzheimer's disease
Biol Psychiatry77, 720-728. PubMed Europe PubMed DOI
D'Avanzo,C., Sliwinski,C., Wagner,S.L., Tanzi,R.E., Kim,D.Y. and Kovacs,D.M.
gamma-Secretase modulators reduce endogenous amyloid beta42 levels in human neural progenitor cells without altering neuronal differentiation
FASEB J29, 3335-3341. PubMed Europe PubMed DOI
De Strooper,B. and Chavez Gutierrez,L.
Learning by failing: ideas and concepts to tackle gamma-secretases in Alzheimer's disease and beyond
Annu Rev Pharmacol Toxicol55, 419-437. PubMed Europe PubMed DOI I
Deng,H., Lv,L., Li,Y., Zhang,C., Meng,F., Pu,Y., Xiao,J., Qian,L., Zhao,W., Liu,Q., Zhang,D., Wang,Y., Zhang,H., He,Y. and Zhu,J.
The miR-193a-3p regulated PSEN1 gene suppresses the multi-chemoresistance of bladder cancer
Biochim Biophys Acta1852, 520-528. PubMed Europe PubMed DOI
Duggan,S.P., Yan,R. and McCarthy,J.V.
A ubiquitin-binding CUE domain in presenilin-1 enables interaction with K63-linked polyubiquitin chains
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Elad,N., De Strooper,B., Lismont,S., Hagen,W., Veugelen,S., Arimon,M., Horre,K., Berezovska,O., Sachse,C. and Chavez-Gutierrez,L.
The dynamic conformational landscape of gamma-secretase
J Cell Sci128, 589-598. PubMed Europe PubMed DOI S
Fischer,C., Zultanski,S.L., Zhou,H., Methot,J.L., Shah,S., Hayashi,I., Hughes,B.L., Moxham,C.M., Bays,N.W., Smotrov,N., Hill,A.D., Pan,B.S., Wu,Z., Moy,L.Y., Tanga,F., Kenific,C., Cruz,J.C., Walker,D., Bouthillette,M., Nikov,G.N., Deshmukh,S.V., Jeliazkova-Mecheva,V.V., Diaz,D., Michener,M.S., Cook,J.J., Munoz,B. and Shearman,M.S.
Discovery of novel triazolobenzazepinones as gamma-secretase modulators with central Abeta42 lowering in rodents and rhesus monkeys
Bioorg Med Chem Lett25, 3488-3494. PubMed Europe PubMed DOI
Fleisher,A.S., Chen,K., Quiroz,Y.T., Jakimovich,L.J., Gutierrez Gomez,M., Langois,C.M., Langbaum,J.B., Roontiva,A., Thiyyagura,P., Lee,W., Ayutyanont,N., Lopez,L., Moreno,S., Munoz,C., Tirado,V., Acosta-Baena,N., Fagan,A.M., Giraldo,M., Garcia,G., Huentelman,M.J., Tariot,P.N., Lopera,F. and Reiman,E.M.
Associations between biomarkers and age in the presenilin 1 E280A autosomal dominant Alzheimer disease kindred: a cross-sectional study
JAMA Neurol72, 316-324. PubMed Europe PubMed DOI M
Jiang,H.Y., Li,G.D., Dai,S.X., Bi,R., Zhang,D.F., Li,Z.F., Xu,X.F., Zhou,T.C., Yu,L. and Yao,Y.G.
Identification of PSEN1 mutations p.M233L and p.R352C in Han Chinese families with early-onset familial Alzheimer's disease
Neurobiol Aging36, e3-e6. PubMed Europe PubMed DOI M
Kamp,F., Winkler,E., Trambauer,J., Ebke,A., Fluhrer,R. and Steiner,H.
Intramembrane proteolysis of beta-amyloid precursor protein by gamma-secretase is an unusually slow process
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Kang,Y., Melcher,K. and Xu,H.E.
The cryo-electron microscopy structure of gamma-secretase: towards complex assembly, substrate recognition and a catalytic mechanism
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Kong,R., Chang,S., Xia,W. and Wong,S.T.
Molecular dynamics simulation study reveals potential substrate entry path into gamma-secretase/presenilin-1
J Struct Biol191, 120-129. PubMed Europe PubMed DOI
Kosik,K.S., Munoz,C., Lopez,L., Arcila,M.L., Garcia,G., Madrigal,L., Moreno,S., Rios Romenets,S., Lopez,H., Gutierrez,M., Langbaum,J.B., Cho,W., Suliman,S., Tariot,P.N., Ho,C., Reiman,E.M. and Lopera,F.
Homozygosity of the autosomal dominant Alzheimer disease presenilin 1 E280A mutation
Neurology84, 206-208. PubMed Europe PubMed DOI M
MacPherson,S.E., Parra,M.A., Moreno,S., Lopera,F. and Della Sala,S.
Dual memory task impairment in E280A presenilin-1 mutation carriers
J Alzheimers Dis44, 481-492. PubMed Europe PubMed DOI M
Marinangeli,C., Tasiaux,B., Opsomer,R., Hage,S., Sodero,A.O., Dewachter,I., Octave,J.N., Smith,S.O., Constantinescu,S.N. and Kienlen-Campard,P.
Presenilin transmembrane domain 8 conserved AxxxAxxxG motifs are required for the activity of the gamma-secretase complex
J Biol Chem290, 7169-7184. PubMed Europe PubMed DOI
Matz,A., Halamoda-Kenzaoui,B., Hamelin,R., Mosser,S., Alattia,J.R., Dimitrov,M., Moniatte,M. and Fraering,P.C.
Identification of new Presenilin-1 phosphosites: implication for gamma-secretase activity and Abeta production
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Potent benzoazepinone gamma-secretase modulators with improved bioavailability
Bioorg Med Chem Lett25, 3495-3500. PubMed Europe PubMed DOI
Muchnik,C., Olivar,N., Dalmasso,M.C., Azurmendi,P.J., Liberczuk,C., Morelli,L. and Brusco,L.I.
Identification of PSEN2 mutation p.N141I in Argentine pedigrees with early-onset familial Alzheimer's disease
Neurobiol Aging36, 2674-2677. PubMed Europe PubMed DOI M
Pasqualon,T., Pruessmeyer,J., Jankowski,V., Babendreyer,A., Groth,E., Schumacher,J., Koenen,A., Weidenfeld,S., Schwarz,N., Denecke,B., Jahr,H., Dreymueller,D., Jankowski,J. and Ludwig,A.
A cytoplasmic C-terminal fragment of syndecan-1 is generated by sequential proteolysis and antagonizes syndecan-1 dependent lung tumor cell migration
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Pellowska,M., Stein,C., Pohland,M., Merk,D., Klein,J., Eckert,G.P., Schubert-Zsilavecz,M. and Wurglics,M.
Pharmacokinetic properties of MH84, a gamma-secretase modulator with PPARgamma agonistic activity
J Pharm Biomed Anal102, 417-424. PubMed Europe PubMed DOI
Pettersson,M., Johnson,D.S., Humphrey,J.M., Butler,T.W., Am Ende,C.W., Fish,B.A., Green,M.E., Kauffman,G.W., Mullins,P.B., O'Donnell,C.J., Stepan,A.F., Stiff,C.M., Subramanyam,C., Tran,T.P., Vetelino,B.C., Yang,E., Xie,L., Bales,K.R., Pustilnik,L.R., Steyn,S.J., Wood,K.M. and Verhoest,P.R.
Design of pyridopyrazine-1,6-dione gamma-secretase modulators that align potency, MDR efflux ratio, and metabolic stability
ACS Med Chem Lett6, 596-601. PubMed Europe PubMed DOI
Pettersson,M., Johnson,D.S., Humphrey,J.M., Am Ende,C.W., Evrard,E., Efremov,I., Kauffman,G.W., Stepan,A.F., Stiff,C.M., Xie,L., Bales,K.R., Hajos-Korcsok,E., Murrey,H.E., Pustilnik,L.R., Steyn,S.J., Wood,K.M. and Verhoest,P.R.
Discovery of indole-derived pyridopyrazine-1,6-dione gamma-secretase modulators that target presenilin
Bioorg Med Chem Lett25, 908-913. PubMed Europe PubMed DOI
Roeber,S., Muller-Sarnowski,F., Kress,J., Edbauer,D., Kuhlmann,T., Tuttelmann,F., Schindler,C., Winter,P., Arzberger,T., Muller,U., Danek,A. and Kretzschmar,H.A.
Three novel presenilin 1 mutations marking the wide spectrum of age at onset and clinical patterns in familial Alzheimer's disease
J Neural Transm (Vienna)122, 1715-1719. PubMed Europe PubMed DOI M
Sun,L., Zhao,L., Yang,G., Yan,C., Zhou,R., Zhou,X., Xie,T., Zhao,Y., Wu,S., Li,X. and Shi,Y.
Structural basis of human gamma-secretase assembly
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Svedruzic,Z.M., Popovic,K. and Sendula-Jengic,V.
Decrease in catalytic capacity of gamma-secretase can facilitate pathogenesis in sporadic and familial Alzheimer's disease
Mol Cell Neurosci67, 55-65. PubMed Europe PubMed DOI M
Takagi-Niidome,S., Sasaki,T., Osawa,S., Sato,T., Morishima,K., Cai,T., Iwatsubo,T. and Tomita,T.
Cooperative roles of hydrophilic loop 1 and the C-terminus of presenilin 1 in the substrate-gating mechanism of gamma-secretase
J Neurosci35, 2646-2656. PubMed Europe PubMed DOI
Takai,T., Hoashi,Y., Tomata,Y., Morimoto,S., Nakamura,M., Watanabe,T., Igari,T. and Koike,T.
Discovery of novel 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine derivatives as gamma-secretase modulators
Bioorg Med Chem Lett25, 4245-4249. PubMed Europe PubMed DOI
Takei,N., Sobu,Y., Kimura,A., Urano,S., Piao,Y., Araki,Y., Taru,H., Yamamoto,T., Hata,S., Nakaya,T. and Suzuki,T.
Cytoplasmic fragment of alcadein alpha generated by regulated intramembrane proteolysis enhances amyloid beta-protein precursor (APP) transport into the late secretory pathway and facilitates APP cleavage
J Biol Chem290, 987-995. PubMed Europe PubMed DOI
Teranishi,Y., Inoue,M., Yamamoto,N.G., Kihara,T., Wiehager,B., Ishikawa,T., Winblad,B., Schedin-Weiss,S., Frykman,S. and Tjernberg,L.O.
Proton myo-inositol cotransporter is a novel gamma-secretase associated protein that regulates Abeta production without affecting Notch cleavage
FEBS J282, 3438-3451. PubMed Europe PubMed DOI
Walter,J.
Twenty years of presenilins-important proteins in health and disease
Mol Med21 Suppl 1, S41-S48. PubMed Europe PubMed DOI V
Wan,J., Li,Y.-X. and Zheng,W.-H.
Research progress in spatial structure and modulators of gamma-secretase
Chin J Pharmacol Toxicol29, 979-985. DOI V
Weissmiller,A.M., Natera-Naranjo,O., Reyna,S.M., Pearn,M.L., Zhao,X., Nguyen,P., Cheng,S., Goldstein,L.S., Tanzi,R.E., Wagner,S.L., Mobley,W.C. and Wu,C.
A gamma-secretase inhibitor, but not a gamma-secretase modulator, induced defects in BDNF axonal trafficking and signaling: evidence for a role for APP
PLoS ONE10, e0118379-e0118379. PubMed Europe PubMed DOI
Wolfe,M.S.
Cutting in on a secretase pas de deux
Cell Res25, 1091-1092. PubMed Europe PubMed DOI
Xia,D., Watanabe,H., Wu,B., Lee,S.H., Li,Y., Tsvetkov,E., Bolshakov,V.Y., Shen,J. and Kelleher,R.J.3.
Presenilin-1 knockin mice reveal loss-of-function mechanism for familial Alzheimer's disease
Neuron85, 967-981. PubMed Europe PubMed DOI M
Zahs,K.R. and Ashe,K.H.
More than a FAD: the in vivo effects of disease-linked presenilin-1 mutations
Neuron85, 893-895. PubMed Europe PubMed DOI M
Zhao,Z., Pissarnitski,D.A., Josien,H.B., Wu,W.L., Xu,R., Li,H., Clader,J.W., Burnett,D.A., Terracina,G., Hyde,L., Lee,J., Song,L., Zhang,L. and Parker,E.M.
Discovery of a novel, potent spirocyclic series of gamma-secretase inhibitors
J Med Chem58, 8806-8817. PubMed Europe PubMed DOI I

2014

Acx,H., Chavez-Gutierrez,L., Serneels,L., Lismont,S., Benurwar,M., Elad,N. and De Strooper,B.
Signature amyloid beta profiles are produced by different gamma-secretase complexes
J Biol Chem289, 4346-4355. PubMed Europe PubMed DOI
Ballard,T., Murrey,H.E., Geoghegan,K.F., Am Ende,C.W. and Johnson,D.S.
Investigating gamma-secretase protein interactions in live cells using active site-directed clickable dual-photoaffinity probes
MedChemComm5, 321-327. DOI I
Bhadoriya,K.S., Sharma,M.C., Sharma,S., Jain,S.V. and Avchar,M.H.
An approach to design potent anti-Alzheimer's agents by 3D-QSAR studies on fused 5,6-bicyclic heterocycles as gamma-secretase modulators using kNN-MFA methodology
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Bolduc,D.M. and Wolfe,M.S.
Structure of nicastrin unveils secrets of gamma-secretase
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Cornejo-Olivas,M.R., Yu,C.E., Mazzetti,P., Mata,I.F., Meza,M., Lindo-Samanamud,S., Leverenz,J.B. and Bird,T.D.
Clinical and molecular studies reveal a PSEN1 mutation (L153V) in a Peruvian family with early-onset Alzheimer's disease
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De Strooper,B.
Lessons from a failed gamma-secretase Alzheimer trial
Cell159, 721-726. PubMed Europe PubMed DOI I
Deng,B., Lian,Y., Wang,X., Zeng,F., Jiao,B., Wang,Y.R., Liang,C.R., Liu,Y.H., Bu,X.L., Yao,X.Q., Zhu,C., Shen,L., Zhou,H.D., Zhang,T. and Wang,Y.J.
Identification of a novel mutation in the presenilin 1 gene in a Chinese Alzheimer's disease family
Neurotox Res26, 211-215. PubMed Europe PubMed DOI M
Dolzhanskaya,N., Gonzalez,M.A., Sperziani,F., Stefl,S., Messing,J., Wen,G.Y., Alexov,E., Zuchner,S. and Velinov,M.
A novel p.Leu(381)Phe mutation in presenilin 1 is associated with very early onset and unusually fast progressing dementia as well as lysosomal inclusions typically seen in Kufs disease
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Gai,J.W., Wahafu,W., Hsieh,Y.C., Liu,M., Zhang,L., Li,S.W., Zhang,B., He,Q., Guo,H. and Jin,J.
Inhibition of presenilins attenuates proliferation and invasion in bladder cancer cells through multiple pathways
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Gertsik,N., Ballard,T.E., Am Ende,C.W., Johnson,D.S. and Li,Y.-M.
Development of CBAP-BPyne, a probe for gamma-secretase and presenilinase
MedChemComm5, 338-341. PubMed Europe PubMed DOI I
Gertsik,N., Chiu,D. and Li,Y.M.
Complex regulation of gamma-secretase: from obligatory to modulatory subunits
Front Aging Neurosci6, 342-342. PubMed Europe PubMed DOI
Groot,A.J., Habets,R., Yahyanejad,S., Hodin,C.M., Reiss,K., Saftig,P., Theys,J. and Vooijs,M.
Regulated proteolysis of NOTCH2 and NOTCH3 receptors by ADAM10 and presenilins
Mol Cell Biol34, 2822-2832. PubMed Europe PubMed DOI
Hall,A. and Patel,T.R.
gamma-Secretase modulators: current status and future directions
Prog Med Chem53, 101-145. PubMed Europe PubMed DOI V
Han,J., Jung,S., Jang,J., Kam,T.I., Choi,H., Kim,B.J., Nah,J., Jo,D.G., Nakagawa,T., Nishimura,M. and Jung,Y.K.
OCIAD2 activates gamma-secretase to enhance amyloid beta production by interacting with nicastrin
Cell Mol Life Sci71, 2561-2576. PubMed Europe PubMed DOI
Holmes,O., Paturi,S., Selkoe,D.J. and Wolfe,M.S.
Pen-2 is essential for gamma-secretase complex stability and trafficking but partially dispensable for endoproteolysis
Biochemistry53, 4393-4406. PubMed Europe PubMed DOI
Jung,J.I., Ran,Y., Cruz,P.E., Rosario,A.M., Ladd,T.B., Kukar,T.L., Koo,E.H., Felsenstein,K.M. and Golde,T.E.
Complex relationships between substrate sequence and sensitivity to alterations in gamma-secretase processivity induced by gamma-secretase modulators
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Klimkowicz-Mrowiec,A., Bodzioch,M., Szczudlik,A. and Slowik,A.
Clinical presentation of early-onset Alzheimer's disease as a result of mutation in exon 12 of the PSEN-1 gene
Am J Alzheimers Dis Other Demen29, 732-734. PubMed Europe PubMed DOI M
Kobayashi,T., Iwama,S., Fusano,A., Kato,Y., Ikeda,A., Teranishi,Y., Nishihara,A. and Tobe,M.
Design and synthesis of an aminopiperidine series of gamma-secretase modulators
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Structural interactions between inhibitor and substrate docking sites give insight into mechanisms of human PS1 complexes
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Li,Y., Bohm,C., Dodd,R., Chen,F., Qamar,S., Schmitt-Ulms,G., Fraser,P.E. and St George-Hyslop,P.H.
Structural biology of presenilin 1 complexes
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Liao,Y.F., Tang,Y.C., Chang,M.Y., Wang,B.J. and Hu,M.K.
Discovery of small molecular (d)-leucinamides as potent, Notch-sparing gamma-secretase modulators
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Lu,P., Bai,X.C., Ma,D., Xie,T., Yan,C., Sun,L., Yang,G., Zhao,Y., Zhou,R., Scheres,S.H. and Shi,Y.
Three-dimensional structure of human gamma-secretase
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Luedecke,D., Becktepe,J.S., Lehmbeck,J.T., Finckh,U., Yamamoto,R., Jahn,H. and Boelmans,K.
A novel presenilin 1 mutation (Ala275Val) as cause of early-onset familial Alzheimer disease
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Meckler,X. and Checler,F.
Visualization of specific gamma-secretase complexes using bimolecular fluorescence complementation
J Alzheimers Dis40, 161-176. PubMed Europe PubMed DOI
Midde,K., Rich,R., Saxena,A., Gryczynski,I., Borejdo,J. and Das,H.K.
Membrane topology of human presenilin-1 in SK-N-SH cells determined by fluorescence correlation spectroscopy and fluorescent energy transfer
Cell Biochem Biophys70, 923-932. PubMed Europe PubMed DOI S
Mitani,Y., Akashiba,H., Saita,K., Yarimizu,J., Uchino,H., Okabe,M., Asai,M., Yamasaki,S., Nozawa,T., Ishikawa,N., Shitaka,Y., Ni,K. and Matsuoka,N.
Pharmacological characterization of the novel gamma-secretase modulator AS2715348, a potential therapy for Alzheimer's disease, in rodents and nonhuman primates
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Molecular mechanism of the intramembrane cleavage of the beta-carboxyl terminal fragment of amyloid precursor protein by gamma-secretase
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A novel presenilin 1 mutation in early-onset Alzheimer's disease with prominent frontal features
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Pettersson,M., Johnson,D.S., Subramanyam,C., Bales,K.R., Am Ende,C.W., Fish,B.A., Green,M.E., Kauffman,G.W., Mullins,P.B., Navaratnam,T., Sakya,S.M., Stiff,C.M., Tran,T.P., Xie,L., Zhang,L., Pustilnik,L.R., Vetelino,B.C., Wood,K.M., Pozdnyakov,N., Verhoest,P.R. and O'Donnell,C.J.
Design, synthesis, and pharmacological evaluation of a novel series of pyridopyrazine-1,6-dione gamma-secretase modulators
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Ajmani,S., Janardhan,S. and Viswanadhan,V.N.
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Sitek,E.J., Narozanska,E., Peplonska,B., Filipek,S., Barczak,A., Styczynska,M., Mlynarczyk,K., Brockhuis,B., Portelius,E., Religa,D., Barcikowska,M., Slawek,J. and Zekanowski,C.
A patient with posterior cortical atrophy possesses a novel mutation in the presenilin 1 gene
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Smolarkiewicz,M., Skrzypczak,T. and Wojtaszek,P.
The very many faces of presenilins and the gamma-secretase complex
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Takagi-Niidome,S., Osawa,S., Tomita,T. and Iwatsubo,T.
Inhibition of gamma-secretase activity by a monoclonal antibody against the extracellular hydrophilic loop of presenilin 1
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Thathiah,A., Horre,K., Snellinx,A., Vandewyer,E., Huang,Y., Ciesielska,M., De Kloe,G., Munck,S. and De Strooper,B.
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Toyn,J.H., Rowley,A., Matsuoka,Y., Tomita,T. and Imbimbo,B.P.
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Wilson,L. and Lardelli,M.
The development of an in vivo gamma-secretase assay using zebrafish embryos
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Structure activity relationship studies of tricyclic bispyran sulfone gamma-secretase inhibitors
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Discovery of a novel [3.2.1] benzo fused bicyclic sulfonamide-pyrazoles as potent, selective and efficacious gamma-secretase inhibitors
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2012

Adeniji,A.O., Wells,R.M. and Adejare,A.
Syntheses and in-vitro evaluation of novel adamantane based gamma-secretase inhibitors
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Design and synthesis of a novel series of bicyclic heterocycles as potent gamma-secretase modulators
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Borgegard,T., Jureus,A., Olsson,F., Rosqvist,S., Sabirsh,A., Rotticci,D., Paulsen,K., Klintenberg,R., Yan,H., Waldman,M., Stromberg,K., Nord,J., Johansson,J., Regner,A., Parpal,S., Malinowsky,D., Radesater,A.C., Li,T., Singh,R., Eriksson,H. and Lundkvist,J.
First and second generation gamma-secretase modulators (GSMs) modulate amyloid-beta (Abeta) peptide production through different mechanisms
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Borroni,B., Pilotto,A., Bonvicini,C., Archetti,S., Alberici,A., Lupi,A., Gennarelli,M. and Padovani,A.
Atypical presentation of a novel Presenilin 1 R377W mutation: Sporadic, late-onset Alzheimer Disease with epilepsy and frontotemporal atrophy
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Cacquevel,M., Aeschbach,L., Houacine,J. and Fraering,P.C.
Alzheimer's disease-linked mutations in presenilin-1 result in a drastic loss of activity in purified gamma-secretase complexes
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Chau,D.M., Crump,C.J., Villa,J.C., Scheinberg,D.A. and Li,Y.M.
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Chavez-Gutierrez,L., Bammens,L., Benilova,I., Vandersteen,A., Benurwar,M., Borgers,M., Lismont,S., Zhou,L., Van Cleynenbreugel,S., Esselmann,H., Wiltfang,J., Serneels,L., Karran,E., Gijsen,H., Schymkowitz,J., Rousseau,F., Broersen,K. and De Strooper,B.
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SAR of tricyclic sulfones as gamma-secretase inhibitors
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2010

Ahn,K., Shelton,C.C., Tian,Y., Zhang,X., Gilchrist,M.L., Sisodia,S.S. and Li,Y.M.
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CHF5074, a novel gamma-secretase modulator, restores hippocampal neurogenesis potential and reverses contextual memory deficit in a transgenic mouse model of Alzheimer's disease
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Modulation of gamma-secretase reduces beta-amyloid deposition in a transgenic mouse model of Alzheimer's disease
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Design, synthesis, and structure-activity relationship studies of N-arylsulfonyl morpholines as gamma-secretase inhibitors
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Discovery of sulfonamide-pyrazole gamma-secretase inhibitors
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Requirement for small side chain residues within the GxGD-motif of presenilin for gamma-secretase substrate cleavage
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Characterization of an atypical gamma-secretase complex from hematopoietic origin
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Purine derivatives as potent gamma-secretase modulators
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Piperazinyl pyrimidine derivatives as potent gamma-secretase modulators
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Are gamma-secretase inhibitors detrimental for Alzheimer's disease patients?
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Sasikumar,T.K., Burnett,D.A., Asberom,T., Wu,W.L., Bennett,C., Cole,D., Xu,R., Greenlee,W.J., Clader,J., Zhang,L. and Hyde,L.
Tetracyclic sulfones as potent gamma-secretase inhibitors: synthesis and structure-activity relationship studies
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Sasikumar,T.K., Qiang,L., Burnett,D.A., Cole,D., Xu,R., Li,H., Greenlee,W.J., Clader,J., Zhang,L. and Hyde,L.
Tricyclic sulfones as orally active gamma-secretase inhibitors: synthesis and structure-activity relationship studies
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Small,D.H., Klaver,D.W. and Foa,L.
Presenilins and the gamma-secretase: still a complex problem
Mol Brain3, 7-7. PubMed Europe PubMed DOI V
Sobhanifar,S., Schneider,B., Lohr,F., Gottstein,D., Ikeya,T., Mlynarczyk,K., Pulawski,W., Ghoshdastider,U., Kolinski,M., Filipek,S., Guntert,P., Bernhard,F. and Dotsch,V.
Structural investigation of the C-terminal catalytic fragment of presenilin 1
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St George-Hyslop,P. and Schmitt-Ulms,G.
Alzheimer's disease: selectively tuning gamma-secretase
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Fluorinated piperidine acetic acids as gamma-secretase modulators
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In vivo reconstitution of gamma-secretase in Drosophila results in substrate specificity
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A GPCR/secretase complex regulates beta- and gamma-secretase specificity for Abeta production and contributes to AD pathogenesis
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An APP inhibitory domain containing the Flemish mutation residue modulates gamma-secretase activity for Abeta production
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Substrate docking to gamma-secretase allows access of gamma-secretase modulators to an allosteric site
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Functional analysis of the transmembrane domains of presenilin 1: participation of transmembrane domains 2 and 6 in the formation of initial substrate-binding site of gamma-secretase
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Evaluation of selective gamma-secretase inhibitor PF-03084014 for its antitumor efficacy and gastrointestinal safety to guide optimal clinical trial design
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Presenilin/gamma-secretase cleaves CD46 in response to Neisseria infection
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Novel gamma-secretase inhibitors uncover a common nucleotide-binding site in JAK3, SIRT2, and PS1
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Design and synthesis of tricyclic sulfones as gamma-secretase inhibitors with greatly reduced Notch toxicity
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Discovery of a novel sulfonamide-pyrazolopiperidine series as potent and efficacious gamma-secretase inhibitors (Part II)
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Discovery of a novel sulfonamide-pyrazolopiperidine series as potent and efficacious gamma-secretase inhibitors
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Familial Alzheimer's disease mutations in presenilin 1 do not alter levels of the secreted amyloid-beta protein precursor generated by beta-secretase cleavage
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2009

Baumann,S., Hottecke,N., Schubenel,R., Baumann,K. and Schmidt,B.
NSAID-derived gamma-secretase modulators. Part III: membrane anchoring
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Shimojo,M., Sahara,N., Mizoroki,T., Funamoto,S., Morishima-Kawashima,M., Kudo,T., Takeda,M., Ihara,Y., Ichinose,H. and Takashima,A.
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Sparey,T., Clarke,E., Hannam,J., Harrison,T., Madin,A., Shearman,M. and Sohal,B.
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Tan,J., Mao,G., Cui,M.Z., Kang,S.C., Lamb,B., Wong,B.S., Sy,M.S. and Xu,X.
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Sodium selenite inhibits gamma-secretase activity through activation of ERK
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van Loo,K.M., Dejaegere,T., van Zweeden,M., van Schijndel,J.E., Wijmenga,C., Trip,M.D. and Martens,G.J.
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2007

Albani,D., Roiter,I., Artuso,V., Batelli,S., Prato,F., Pesaresi,M., Galimberti,D., Scarpini,E., Bruni,A., Franceschi,M., Piras,M.R., Confaloni,A. and Forloni,G.
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Discovery of gamma-secretase inhibitors efficacious in a transgenic animal model of Alzheimer's disease
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Best,J.D., Smith,D.W., Reilly,M.A., O'Donnell,R., Lewis,H.D., Ellis,S., Wilkie,N., Rosahl,T.W., Laroque,P.A., Boussiquet-Leroux,C., Churcher,I., Atack,J.R., Harrison,T. and Shearman,M.S.
The novel gamma secretase inhibitor N-[cis-4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)cyclohexyl]-1,1, 1-trifluoromethanesulfonamide (MRK-560) reduces amyloid plaque deposition without evidence of notch-related pathology in the Tg2576 mouse
J Pharmacol Exp Ther320, 552-558. PubMed Europe PubMed DOI I
Bojarski,L., Lewandowicz,A., Blazejczyk,M., Sobczak,A., Kuznicki,J. and Wojda,U.
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Thiazole-diamides as potent gamma-secretase inhibitors
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Czirr,E., Leuchtenberger,S., Dorner-Ciossek,C., Schneider,A., Jucker,M., Koo,E.H., Pietrzik,C.U., Baumann,K. and Weggen,S.
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Davies,A.J., Scott,J.P., Bishop,B.C., Brands,K.M., Brewer,S.E., Dasilva,J.O., Dormer,P.G., Dolling,U.H., Gibb,A.D., Hammond,D.C., Lieberman,D.R., Palucki,M. and Payack,J.F.
A novel crystallization-induced diastereomeric transformation based on a reversible carbon-sulfur bond formation. Application to the synthesis of a gamma-secretase inhibitor
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Fuwa,H., Takahashi,Y., Konno,Y., Watanabe,N., Miyashita,H., Sasaki,M., Natsugari,H., Kan,T., Fukuyama,T., Tomita,T. and Iwatsubo,T.
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Guo,T., Gu,H., Hobbs,D.W., Rokosz,L.L., Stauffer,T.M., Jacob,B. and Clader,J.W.
Design, synthesis, and evaluation of tetrahydroquinoline and pyrrolidine sulfonamide carbamates as gamma-secretase inhibitors
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Hatchett,C.S., Tyler,S., Armstrong,D., Dawbarn,D. and Allen,S.J.
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Herzig,M.C., Paganetti,P., Staufenbiel,M. and Jucker,M.
BACE1 and mutated presenilin-1 differently modulate Abeta40 and Abeta42 levels and cerebral amyloidosis in APPDutch transgenic mice
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1-(3',4'-Dichloro-2-fluoro[1,1'-biphenyl]-4-yl)-cyclopropanecarboxylic acid (CHF5074), a novel gamma-secretase modulator, reduces brain beta-amyloid pathology in a transgenic mouse model of Alzheimer's disease without causing peripheral toxicity
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Isoo,N., Sato,C., Miyashita,H., Shinohara,M., Takasugi,N., Morohashi,Y., Tsuji,S., Tomita,T. and Iwatsubo,T.
Abeta42 overproduction associated with structural changes in the catalytic pore of gamma-secretase: common effects of Pen-2 N-terminal elongation and fenofibrate
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Small conformationally restricted piperidine N-arylsulfonamides as orally active gamma-secretase inhibitors
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Kauwe,J.S., Jacquart,S., Chakraverty,S., Wang,J., Mayo,K., Fagan,A.M., Holtzman,D.M., Morris,J.C. and Goate,A.M.
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gamma-Secretase inhibitors suppress the growth of leukemia and lymphoma cells
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Kuzuya,A., Uemura,K., Kitagawa,N., Aoyagi,N., Kihara,T., Ninomiya,H., Ishiura,S., Takahashi,R. and Shimohama,S.
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Discovery of 2,4,6-trisubstituted N-arylsulfonyl piperidines as gamma-secretase inhibitors
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Li,T., Wen,H., Brayton,C., Das,P., Smithson,L.A., Fauq,A., Fan,X., Crain,B.J., Price,D.L., Golde,T.E., Eberhart,C.G. and Wong,P.C.
Epidermal growth factor receptor and notch pathways participate in the tumor suppressor function of gamma-secretase
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Moderate reduction of gamma-secretase attenuates amyloid burden and limits mechanism-based liabilities
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Liao,Y.F., Wang,B.J., Hsu,W.M., Lee,H., Liao,C.Y., Wu,S.Y., Cheng,H.T. and Hu,M.K.
Unnatural amino acid-substituted (hydroxyethyl)urea peptidomimetics inhibit gamma-secretase and promote the neuronal differentiation of neuroblastoma cells
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Lundkvist,J. and Naslund,J.
gamma-Secretase: a complex target for Alzheimer's disease
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Madsen,L.B., Thomsen,B., Larsen,K., Bendixen,C., Holm,I.E., Fredholm,M., Jorgensen,A.L. and Nielsen,A.L.
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Narlawar,R., Perez Revuelta,B.I., Baumann,K., Schubenel,R., Haass,C., Steiner,H. and Schmidt,B.
N-Substituted carbazolyloxyacetic acids modulate Alzheimer associated gamma-secretase
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N-(5-Chloro-2-(hydroxymethyl)-N-alkyl-arylsulfonamides as gamma-secretase inhibitors
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Parks,A.L. and Curtis,D.
Presenilin diversifies its portfolio
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Peters,J.U., Galley,G., Jacobsen,H., Czech,C., David-Pierson,P., Kitas,E.A. and Ozmen,L.
Novel orally active, dibenzazepinone-based gamma-secretase inhibitors
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2,6-Disubstituted N-arylsulfonyl piperidines as gamma-secretase inhibitors
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Prager,K., Wang-Eckhardt,L., Fluhrer,R., Killick,R., Barth,E., Hampel,H., Haass,C. and Walter,J.
A structural switch of presenilin 1 by glycogen synthase kinase 3beta-mediated phosphorylation regulates the interaction with beta-catenin and its nuclear signaling
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Discovery of (S)-2-((S)-2-(3,5-difluorophenyl)-2-hydroxyacetamido)-N-((S,Z)-3-methyl-4- oxo-4,5-dihydro-3H-benzo[d][1,2]diazepin-5-yl)propanamide (BMS-433796): a gamma-secretase inhibitor with Abeta lowering activity in a transgenic mouse model of Alzheimer's disease
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Raman,A., Lin,X., Suri,M., Hewitt,M., Constantinescu,C.S. and Phillips,M.F.
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When loss is gain: reduced presenilin proteolytic function leads to increased Abeta42/Abeta40. Talking Point on the role of presenilin mutations in Alzheimer disease
EMBO Rep8, 136-140. PubMed Europe PubMed DOI
Wolfe,M.S.
gamma-Secretase modulators
Curr Alzheimer Res4, 571-573. PubMed Europe PubMed DOI
Xiong,K., Clough,R.W., Luo,X.G., Struble,R.G., Li,Y.M. and Yan,X.X.
[3H]-L-685,458 as a radiotracer that maps gamma-secretase complex in the rat brain: relevance to Abeta genesis and presence of active presenilin-1 components
Brain Res1157, 81-91. PubMed Europe PubMed DOI I
Yang,M.G., Shi,J.L., Modi,D.P., Wells,J., Cochran,B.M., Wolf,M.A., Thompson,L.A., Ramanjulu,M.M., Roach,A.H., Zaczek,R., Robertson,D.W., Wexler,R.R. and Olson,R.E.
Design and synthesis of benzoazepinone-derived cyclic malonamides and aminoamides as potent gamma-secretase inhibitors
Bioorg Med Chem Lett17, 3910-3915. PubMed Europe PubMed DOI I
Yin,Y.I., Bassit,B., Zhu,L., Yang,X., Wang,C. and Li,Y.M.
gamma-Secretase substrate concentration modulates the Abeta42/Abeta40 ratio: implications for Alzheimer disease
J Biol Chem282, 23639-23644. PubMed Europe PubMed DOI
Zhang,Y.W., Wang,R., Liu,Q., Zhang,H., Liao,F.F. and Xu,H.
Presenilin/gamma-secretase-dependent processing of beta-amyloid precursor protein regulates EGF receptor expression
Proc Natl Acad Sci U S A104, 10613-10618. PubMed Europe PubMed DOI
Zhao,G., Tan,J., Mao,G., Cui,M.Z. and Xu,X.
The same gamma-secretase accounts for the multiple intramembrane cleavages of APP
J Neurochem100, 1234-1246. PubMed Europe PubMed DOI I
Zhou,S., Zhou,H., Walian,P.J. and Jap,B.K.
Regulation of gamma-secretase activity in Alzheimer's disease
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2006

[YEAR:7-5-2006]Arumugam,T.V., Chan,S.L., Jo,D.G., Yilmaz,G., Tang,S.C., Cheng,A., Gleichmann,M., Okun,E., Dixit,V.D., Chigurupati,S., Mughal,M.R., Ouyang,X., Miele,L., Magnus,T., Poosala,S., Granger,D.N. and Mattson,M.P.
Gamma secretase-mediated Notch signaling worsens brain damage and functional outcome in ischemic stroke
Nat Med12, 621-623. PubMed Europe PubMed DOI
Avram,S., Milac,A.L., Mihailescu,D.F., Dabu,A. and Flonta,M.L.
Computer-aided drug design applied to beta and gamma secretase inhibitors - perspectives for new Alzheimer disease therapy
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[YEAR:9-1-2006]Bentahir,M., Nyabi,O., Verhamme,J., Tolia,A., Horre,K., Wiltfang,J., Esselmann,H. and De Strooper,B.
Presenilin clinical mutations can affect gamma-secretase activity by different mechanisms
J Neurochem96, 732-742. PubMed Europe PubMed DOI
[YEAR:27-1-2006]Best,J.D., Jay,M.T., Otu,F., Churcher,I., Reilly,M., Morentin-Gutierrez,P., Pattison,C., Harrison,T., Shearman,M.S. and Atack,J.R.
In vivo characterization of Abeta(40) changes in brain and cerebrospinal fluid using the novel gamma-secretase inhibitor N-[cis-4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)cyclohexyl]-1,1, 1-trifluoromethanesulfonamide (MRK-560) in the rat
J Pharmacol Exp Ther317, 786-790. PubMed Europe PubMed DOI I
[YEAR:21-11-2006]Chandu,D., Huppert,S.S. and Kopan,R.
Analysis of transmembrane domain mutants is consistent with sequential cleavage of Notch by gamma-secretase
J Neurochem96, 228-235. PubMed Europe PubMed DOI
[YEAR:27-4-2006]Chen,F., Hasegawa,H., Schmitt-Ulms,G., Kawarai,T., Bohm,C., Katayama,T., Gu,Y., Sanjo,N., Glista,M., Rogaeva,E., Wakutani,Y., Pardossi-Piquard,R., Ruan,X., Tandon,A., Checler,F., Marambaud,P., Hansen,K., Westaway,D., St George-Hyslop,P. and Fraser,P.
TMP21 is a presenilin complex component that modulates gamma-secretase but not epsilon-secretase activity
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[YEAR:2-11-2006]Churcher,I., Beher,D., Best,J.D., Castro,J.L., Clarke,E.E., Gentry,A., Harrison,T., Hitzel,L., Kay,E., Kerrad,S., Lewis,H.D., Morentin-Gutierrez,P., Mortishire-Smith,R., Oakley,P.J., Reilly,M., Shaw,D.E., Shearman,M.S., Teall,M.R., Williams,S. and Wrigley,J.D.
4-Substituted cyclohexyl sulfones as potent, orally active gamma-secretase inhibitors
Bioorg Med Chem Lett16, 280-284. PubMed Europe PubMed DOI I
[YEAR:11-8-2006]Clarke,E.E., Churcher,I., Ellis,S., Wrigley,J.D., Lewis,H.D., Harrison,T., Shearman,M.S. and Beher,D.
Intra- or intercomplex binding to the gamma-secretase enzyme. A model to differentiate inhibitor classes
J Biol Chem281, 31279-31289. PubMed Europe PubMed DOI I
[YEAR:25-10-2006]Coolen,M.W., van Loo,K.M., van Bakel,N.N., Ellenbroek,B.A., Cools,A.R. and Martens,G.J.
Reduced Aph-1b expression causes tissue- and substrate-specific changes in gamma-secretase activity in rats with a complex phenotype
FASEB J20, 175-177. PubMed Europe PubMed DOI
[YEAR:5-4-2006]Deng,Y., Tarassishin,L., Kallhoff,V., Peethumnongsin,E., Wu,L., Li,Y.M. and Zheng,H.
Deletion of presenilin 1 hydrophilic loop sequence leads to impaired gamma-secretase activity and exacerbated amyloid pathology
J Neurosci26, 3845-3854. PubMed Europe PubMed DOI
Dewji,N.N.
Presenilin structure in mechanisms leading to Alzheimer's disease
J Alzheimers Dis10, 277-290. PubMed Europe PubMed
El Mouedden,M., Vandermeeren,M., Meert,T. and Mercken,M.
Reduction of Abeta levels in the Sprague Dawley rat after oral administration of the functional gamma-secretase inhibitor, DAPT: a novel non-transgenic model for Abeta production inhibitors
Curr Pharm Des12, 671-676. PubMed Europe PubMed DOI I
Evin,G., Sernee,M.F. and Masters,C.L.
Inhibition of gamma-secretase as a therapeutic intervention for Alzheimer's disease: prospects, limitations and strategies
CNS Drugs20, 351-372. PubMed Europe PubMed DOI I
[YEAR:18-4-2006]Fukumori,A., Okochi,M., Tagami,S., Jiang,J., Itoh,N., Nakayama,T., Yanagida,K., Ishizuka-Katsura,Y., Morihara,T., Kamino,K., Tanaka,T., Kudo,T., Tanii,H., Ikuta,A., Haass,C. and Takeda,M.
Presenilin-dependent gamma-secretase on plasma membrane and endosomes is functionally distinct
Biochemistry45, 4907-4914. PubMed Europe PubMed DOI
[YEAR:9-6-2006]Fuwa,H., Hiromoto,K., Takahashi,Y., Yokoshima,S., Kan,T., Fukuyama,T., Iwatsubo,T., Tomita,T. and Natsugari,H.
Synthesis of biotinylated photoaffinity probes based on arylsulfonamide gamma-secretase inhibitors
Bioorg Med Chem Lett16, 4184-4189. PubMed Europe PubMed DOI I
[YEAR:10-2-2006]Herl,L., Lleo,A., Thomas,A.V., Nyborg,A.C., Jansen,K., Golde,T.E., Hyman,B.T. and Berezovska,O.
Detection of presenilin-1 homodimer formation in intact cells using fluorescent lifetime imaging microscopy
Biochem Biophys Res Commun340, 668-674. PubMed Europe PubMed DOI
Herranz,H., Stamataki,E., Feiguin,F. and Milan,M.
Self-refinement of Notch activity through the transmembrane protein Crumbs: modulation of gamma-secretase activity
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3-Substituted gem-cyclohexane sulfone based gamma-secretase inhibitors for Alzheimer's disease: conformational analysis and biological activity
Bioorg Med Chem Lett16, 3839-3842. PubMed Europe PubMed DOI I
Kaether,C., Haass,C. and Steiner,H.
Assembly, trafficking and function of gamma-secretase
Neurodegener Dis3, 275-283. PubMed Europe PubMed DOI
[YEAR:4-4-2006]Kakuda,N., Funamoto,S., Yagishita,S., Takami,M., Osawa,S., Dohmae,N. and Ihara,Y.
Equimolar production of amyloid beta-protein and amyloid precursor protein intracellular domain from beta-carboxyl-terminal fragment by gamma-secretase
J Biol Chem281, 14776-14786. PubMed Europe PubMed DOI
[YEAR:25-4-2006]Keller,P.C., Tomita,T., Hayashi,I., Chandu,D., Weber,J.D., Cistola,D.P. and Kopan,R.
A faster migrating variant masquerades as NICD when performing in vitro gamma-secretase assays with bacterially expressed notch substrates
Biochemistry45, 5351-5358. PubMed Europe PubMed DOI A
[YEAR:20-6-2006]Kornilova,A.Y., Kim,J., Laudon,H. and Wolfe,M.S.
Deducing the transmembrane domain organization of presenilin-1 in gamma-secretase by cysteine disulfide cross-linking
Biochemistry45, 7598-7604. PubMed Europe PubMed DOI
[YEAR:4-11-2006]Larner,A.J. and Doran,M.
Clinical phenotypic heterogeneity of Alzheimer's disease associated with mutations of the presenilin-1 gene
J Neurol253, 139-158. PubMed Europe PubMed DOI M
[YEAR:2-5-2006]Lazarov,V.K., Fraering,P.C., Ye,W., Wolfe,M.S., Selkoe,D.J. and Li,H.
Electron microscopic structure of purified, active gamma-secretase reveals an aqueous intramembrane chamber and two pores
Proc Natl Acad Sci U S A103, 6889-6894. PubMed Europe PubMed DOI S
[YEAR:28-3-2006]Morohashi,Y., Kan,T., Tominari,Y., Fuwa,H., Okamura,Y., Watanabe,N., Sato,C., Natsugari,H., Fukuyama,T., Iwatsubo,T. and Tomita,T.
C-terminal fragment of presenilin is the molecular target of a dipeptidic gamma-secretase-specific inhibitor DAPT (N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester)
J Biol Chem281, 14670-14676. PubMed Europe PubMed DOI I
[YEAR:28-12-2006]Narlawar,R., Perez Revuelta,B.I., Haass,C., Steiner,H., Schmidt,B. and Baumann,K.
Scaffold of the cyclooxygenase-2 (COX-2) inhibitor carprofen provides Alzheimer gamma-secretase modulators
J Med Chem49, 7588-7591. PubMed Europe PubMed DOI
Ni,Y., Zhao,X., Bao,G., Zou,L., Teng,L., Wang,Z., Song,M., Xiong,J., Bai,Y. and Pei,G.
Activation of beta2-adrenergic receptor stimulates gamma-secretase activity and accelerates amyloid plaque formation
Nat Med12, 1390-1396. PubMed Europe PubMed DOI
Nyborg,A.C., Ladd,T.B., Zwizinski,C.W., Lah,J.J. and Golde,T.E.
Sortilin, SorCS1b, and SorLA Vps10p sorting receptors, are novel gamma-secretase substrates
Mol Neurodegener1, 3-3. PubMed Europe PubMed DOI
[YEAR:5-5-2006]Ogura,T., Mio,K., Hayashi,I., Miyashita,H., Fukuda,R., Kopan,R., Kodama,T., Hamakubo,T., Iwastubo,T., Tomita,T. and Sato,C.
Three-dimensional structure of the gamma-secretase complex
Biochem Biophys Res Commun343, 525-534. PubMed Europe PubMed DOI
[YEAR:30-5-2006]Oh,Y.S. and Turner,R.J.
Protease digestion indicates that endogenous presenilin 1 is present in at least two physical forms
Biochem Biophys Res Commun346, 330-334. PubMed Europe PubMed DOI
[YEAR:15-11-2006]Sato,C., Morohashi,Y., Tomita,T. and Iwatsubo,T.
Structure of the catalytic pore of gamma-secretase probed by the accessibility of substituted cysteines
J Neurosci26, 12081-12088. PubMed Europe PubMed DOI
Schmidt,B., Baumann,S., Braun,H.A. and Larbig,G.
Inhibitors and modulators of beta- and gamma-secretase
Curr Top Med Chem6, 377-392. PubMed Europe PubMed DOI I
[YEAR:1-6-2006]Shaw,D., Best,J., Dinnell,K., Nadin,A., Shearman,M., Pattison,C., Peachey,J., Reilly,M., Williams,B., Wrigley,J. and Harrison,T.
3,4-Fused cyclohexyl sulfones as gamma-secretase inhibitors
Bioorg Med Chem Lett16, 3073-3077. PubMed Europe PubMed DOI I
Shiraishi,H., Marutani,T., Wang,H.Q., Maeda,Y., Kurono,Y., Takashima,A., Araki,W., Nishimura,M., Yanagisawa,K. and Komano,H.
Reconstitution of gamma-secretase by truncated presenilin (PS) fragments revealed that PS C-terminal transmembrane domain is critical for formation of gamma-secretase complex
Genes Cells11, 83-93. PubMed Europe PubMed DOI
[YEAR:28-2-2006]Siemers,E.R., Quinn,J.F., Kaye,J., Farlow,M.R., Porsteinsson,A., Tariot,P., Zoulnouni,P., Galvin,J.E., Holtzman,D.M., Knopman,D.S., Satterwhite,J., Gonzales,C., Dean,R.A. and May,P.C.
Effects of a gamma-secretase inhibitor in a randomized study of patients with Alzheimer disease
Neurology66, 602-604. PubMed Europe PubMed DOI I
[YEAR:14-7-2006]Spasic,D., Tolia,A., Dillen,K., Baert,V., De Strooper,B., Vrijens,S. and Annaert,W.
Presenilin-1 maintains a nine-transmembrane topology throughout the secretory pathway
J Biol Chem281, 26569-26577. PubMed Europe PubMed DOI
[YEAR:29-10-2006]Stachel,S.J., Coburn,C.A., Steele,T.G., Crouthamel,M.C., Pietrak,B.L., Lai,M.T., Holloway,M.K., Munshi,S.K., Graham,S.L. and Vacca,J.P.
Conformationally biased P3 amide replacements of beta-secretase inhibitors
Bioorg Med Chem Lett16, 641-644. PubMed Europe PubMed DOI I
[YEAR:3-8-2006]Steiner,H., Than,M., Bode,W. and Haass,C.
Pore-forming scissors? A first structural glimpse of gamma-secretase
Trends Biochem Sci31, 491-493. PubMed Europe PubMed DOI S
[YEAR:6-5-2006]Takahashi,Y., Fuwa,H., Kaneko,A., Sasaki,M., Yokoshima,S., Koizumi,H., Takebe,T., Kan,T., Iwatsubo,T., Tomita,T., Natsugari,H. and Fukuyama,T.
Novel gamma-secretase inhibitors discovered by library screening of in-house synthetic natural product intermediates
Bioorg Med Chem Lett16, 3813-3816. PubMed Europe PubMed DOI I
[YEAR:9-2-2006]Thompson,L.A., Liauw,A.Y., Ramanjulu,M.M., Kasireddy-Polam,P., Mercer,S.E., Maduskuie,T.P., Glicksman,M., Roach,A.H., Meredith,J.E., Liu,R.Q., Combs,A.P., Higaki,J.N., Cordell,B., Seiffert,D., Zaczek,R.C., Robertson,D.W. and Olson,R.E.
Synthesis and evaluation of succinoyl-caprolactam gamma-secretase inhibitors
Bioorg Med Chem Lett16, 2357-2363. PubMed Europe PubMed DOI I
Tolia,A., Chavez-Gutierrez,L. and De Strooper,B.
Contribution of presenilin transmembrane domains 6 and 7 to a water-containing cavity in the gamma-secretase complex
J Biol Chem281, 27633-27642. PubMed Europe PubMed DOI
Tomita,T., Tanaka,S., Morohashi,Y. and Iwatsubo,T.
Presenilin-dependent intramembrane cleavage of ephrin-B1
Mol Neurodegener1, 2-2. PubMed Europe PubMed DOI
Tomita,T. and Iwatsubo,T.
gamma-Secretase as a therapeutic target for treatment of Alzheimer's disease
Curr Pharm Des12, 661-670. PubMed Europe PubMed DOI
[YEAR:23-11-2006]Wang,J., Beher,D., Nyborg,A.C., Shearman,M.S., Golde,T.E. and Goate,A.
C-terminal PAL motif of presenilin and presenilin homologues required for normal active site conformation
J Neurochem96, 218-227. PubMed Europe PubMed DOI I
Wolfe,M.S.
Presenilin/gamma-secretase as a therapeutic target
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Wolfe,M.S.
Alzheimer protease hitches a ride
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[YEAR:4-7-2006]Wolfe,M.S.
The gamma-secretase complex: membrane-embedded proteolytic ensemble
Biochemistry45, 7931-7939. PubMed Europe PubMed DOI V
[YEAR:28-3-2006]Yagishita,S., Morishima-Kawashima,M., Tanimura,Y., Ishiura,S. and Ihara,Y.
DAPT-Induced intracellular accumulations of longer amyloid beta-proteins: further implications for the mechanism of intramembrane cleavage by gamma-secretase
Biochemistry45, 3952-3960. PubMed Europe PubMed DOI I
[YEAR:5-4-2006]Yamasaki,A., Eimer,S., Okochi,M., Smialowska,A., Kaether,C., Baumeister,R., Haass,C. and Steiner,H.
The GxGD motif of presenilin contributes to catalytic function and substrate identification of gamma-secretase
J Neurosci26, 3821-3828. PubMed Europe PubMed DOI
[YEAR:27-4-2006]Zhang,M., Haapasalo,A., Kim,D.Y., Ingano,L.A., Pettingell,W.H. and Kovacs,D.M.
Presenilin/gamma-secretase activity regulates protein clearance from the endocytic recycling compartment
FASEB J20, 1176-1178. PubMed Europe PubMed DOI

2005

[YEAR:15-2-2005]Anderson,J.J., Holtz,G., Baskin,P.P., Turner,M., Rowe,B., Wang,B., Kounnas,M.Z., Lamb,B.T., Barten,D., Felsenstein,K., McDonald,I., Srinivasan,K., Munoz,B. and Wagner,S.L.
Reductions in beta-amyloid concentrations in vivo by the gamma-secretase inhibitors BMS-289948 and BMS-299897
Biochem Pharmacol69, 689-698. PubMed Europe PubMed DOI I
[YEAR:27-9-2005]Barten,D.M., Guss,V.L., Corsa,J.A., Loo,A., Hansel,S.B., Zheng,M., Munoz,B., Srinivasan,K., Wang,B., Robertson,B.J., Polson,C.T., Wang,J., Roberts,S.B., Hendrick,J.P., Anderson,J.J., Loy,J.K., Denton,R., Verdoorn,T.A., Smith,D.W. and Felsenstein,K.M.
Dynamics of {beta}-amyloid reductions in brain, cerebrospinal fluid, and plasma of {beta}-amyloid precursor protein transgenic mice treated with a {gamma}-secretase inhibitor
J Pharmacol Exp Ther312, 635-643. PubMed Europe PubMed DOI I
[YEAR:2-3-2005]Best,J.D., Jay,M.T., Otu,F., Ma,J., Nadin,A., Ellis,S., Lewis,H.D., Pattison,C., Reilly,M., Harrison,T., Shearman,M.S., Williamson,T.L. and Atack,J.R.
Quantitative measurement of changes in amyloid-beta(40) in the rat brain and cerebrospinal fluid following treatment with the gamma-secretase inhibitor LY-411575 [N2-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-N1-[(7S)-5-methyl-6-ox o-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-L-alaninamide]
J Pharmacol Exp Ther313, 902-908. PubMed Europe PubMed DOI I
Brunkan,A.L., Martinez,M., Wang,J., Walker,E.S. and Goate,A.M.
A domain at the C-terminus of PS1 is required for presenilinase and gamma-secretase activities
J Neurochem92, 1158-1169. PubMed Europe PubMed DOI
Brunkan,A.L., Martinez,M., Walker,E.S. and Goate,A.M.
Presenilin endoproteolysis is an intramolecular cleavage
Mol Cell Neurosci29, 65-73. PubMed Europe PubMed DOI
Brunkan,A.L. and Goate,A.M.
Presenilin function and gamma-secretase activity
J Neurochem93, 769-792. PubMed Europe PubMed DOI V
[YEAR:10-12-2005]Capell,A., Beher,D., Prokop,S., Steiner,H., Kaether,C., Shearman,M.S. and Haass,C.
Gamma-secretase complex assembly within the early secretory pathway
J Biol Chem280, 6471-6478. PubMed Europe PubMed DOI
Churcher,I. and Beher,D.
Gamma-secretase as a therapeutic target for the treatment of Alzheimer's disease
Curr Pharm Des11, 3363-3382. PubMed Europe PubMed DOI V
[YEAR:29-11-2005]Chyung,J.H., Raper,D.M. and Selkoe,D.J.
gamma-Secretase exists on the plasma membrane as an intact complex that accepts substrates and effects intramembrane cleavage
J Biol Chem280, 4383-4392. PubMed Europe PubMed DOI
[YEAR:2-3-2005]Cowan,J.W., Wang,X., Guan,R., He,K., Jiang,J., Baumann,G., Black,R.A., Wolfe,M.S. and Frank,S.J.
Growth hormone receptor is a target for presenilin-dependent gamma-secretase cleavage
J Biol Chem280, 19331-19342. PubMed Europe PubMed DOI I
[YEAR:12-8-2005]De Strooper,B.
Nicastrin: gatekeeper of the gamma-secretase complex
Cell122, 318-320. PubMed Europe PubMed DOI
[YEAR:19-10-2005]Fraering,P.C., Ye,W., LaVoie,M.J., Ostaszewski,B.L., Selkoe,D.J. and Wolfe,M.S.
gamma-Secretase substrate selectivity can be modulated directly via interaction with a nucleotide-binding site
J Biol Chem280, 41987-41996. PubMed Europe PubMed DOI
Grimwood,S., Hogg,J., Jay,M.T., Lad,A.M., Lee,V., Murray,F., Peachey,J., Townend,T., Vithlani,M., Beher,D., Shearman,M.S. and Hutson,P.H.
Determination of guinea-pig cortical gamma-secretase activity ex vivo following the systemic administration of a gamma-secretase inhibitor
Neuropharmacology48, 1002-1011. PubMed Europe PubMed DOI I
[YEAR:1-4-2005]Gundersen,E., Fan,K., Haas,K., Huryn,D., Steven Jacobsen,J., Kreft,A., Martone,R., Mayer,S., Sonnenberg-Reines,J., Sun,S.C. and Zhou,H.
Molecular-modeling based design, synthesis, and activity of substituted piperidines as gamma-secretase inhibitors
Bioorg Med Chem Lett15, 1891-1894. PubMed Europe PubMed DOI I
Hansson,E.M., Stromberg,K., Bergstedt,S., Yu,G., Naslund,J., Lundkvist,J. and Lendahl,U.
Aph-1 interacts at the cell surface with proteins in the active gamma-secretase complex and membrane-tethered Notch
J Neurochem92, 1010-1020. PubMed Europe PubMed DOI
Henricson,A., Kall,L. and Sonnhammer,E.L.
A novel transmembrane topology of presenilin based on reconciling experimental and computational evidence
FEBS J272, 2727-2733. PubMed Europe PubMed DOI
Hoke,D.E., Tan,J.L., Ilaya,N.T., Culvenor,J.G., Smith,S.J., White,A.R., Masters,C.L. and Evin,G.M.
In vitro gamma-secretase cleavage of the Alzheimer's amyloid precursor protein correlates to a subset of presenilin complexes and is inhibited by zinc
FEBS J272, 5544-5557. PubMed Europe PubMed DOI
Hu,M.K., Liao,Y.F., Wang,B.J., Huang,S.Y. and Liao,C.Y.
gamma-Secretase inhibition of dipeptide-based aldehydes with optimized N-terminal building blocks
Chin Pharm J57, 89-98. I
Huppert,S.S., Ilagan,M.X., De Strooper,B. and Kopan,R.
Analysis of Notch function in presomitic mesoderm suggests a gamma-secretase-independent role for presenilins in somite differentiation
Dev Cell8, 677-688. PubMed Europe PubMed DOI
[YEAR:29-3-2005]Kim,H., Ki,H., Park,H.S. and Kim,K.
Presenilin-1 D257A and D385A mutants fail to cleave Notch in their endoproteolyzed forms, but only presenilin-1 D385A mutant can restore its gamma-secretase activity with the compensatory overexpression of normal C-terminal fragment
J Biol Chem280, 22462-22472. PubMed Europe PubMed DOI
[YEAR:10-11-2005]Kim,S.H. and Sisodia,S.S.
A sequence within the first transmembrane domain of PEN-2 is critical for PEN-2-mediated endoproteolysis of presenilin 1
J Biol Chem280, 1992-2001. PubMed Europe PubMed DOI
[YEAR:1-3-2005]Kornilova,A.Y., Bihel,F., Das,C. and Wolfe,M.S.
The initial substrate-binding site of gamma-secretase is located on presenilin near the active site
Proc Natl Acad Sci U S A102, 3230-3235. PubMed Europe PubMed DOI
[YEAR:21-2-2005]Laras,Y., Quelever,G., Garino,C., Pietrancosta,N., Sheha,M., Bihel,F., Wolfe,M.S. and Kraus,J.L.
Substituted thiazolamide coupled to a redox delivery system: a new gamma-secretase inhibitor with enhanced pharmacokinetic profile
Org Biomol Chem3, 612-618. PubMed Europe PubMed DOI I
[YEAR:25-7-2005]Laudon,H., Hansson,E.M., Melen,K., Bergman,A., Farmery,M.R., Winblad,B., Lendahl,U., von Heijne,G. and Naslund,J.
A nine-transmembrane domain topology for presenilin 1
J Biol Chem280, 35352-35360. PubMed Europe PubMed DOI
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A novel series of potent gamma-secretase inhibitors based on a benzobicyclo[4.2.1]nonane core
Bioorg Med Chem Lett15, 373-378. PubMed Europe PubMed DOI I
[YEAR:21-6-2005]Mastrangelo,P., Mathews,P.M., Chishti,M.A., Schmidt,S.D., Gu,Y., Yang,J., Mazzella,M.J., Coomaraswamy,J., Horne,P., Strome,B., Pelly,H., Levesque,G., Ebeling,C., Jiang,Y., Nixon,R.A., Rozmahel,R., Fraser,P.E., St George-Hyslop,P., Carlson,G.A. and Westaway,D.
Dissociated phenotypes in presenilin transgenic mice define functionally distinct gamma-secretases
Proc Natl Acad Sci U S A102, 8972-8977. PubMed Europe PubMed DOI
Nakaya,Y., Yamane,T., Shiraishi,H., Wang,H.Q., Matsubara,E., Sato,T., Dolios,G., Wang,R., De Strooper,B., Shoji,M., Komano,H., Yanagisawa,K., Ihara,Y., Fraser,P., St George-Hyslop,P. and Nishimura,M.
Random mutagenesis of presenilin-1 identifies novel mutants exclusively generating long amyloid beta-peptides
J Biol Chem280, 19070-19077. PubMed Europe PubMed DOI I
[YEAR:20-4-2005]Oh,Y.S. and Turner,R.J.
Evidence that the COOH terminus of human presenilin 1 is located in extracytoplasmic space
Am J Physiol Cell Physiol289, C576-C581. PubMed Europe PubMed DOI
[YEAR:6-9-2005]Oh,Y.S. and Turner,R.J.
Topology of the C-terminal fragment of human presenilin 1
Biochemistry44, 11821-11828. PubMed Europe PubMed DOI
[YEAR:19-5-2005]Pardossi-Piquard,R., Petit,A., Kawarai,T., Sunyach,C., Alves da Costa,C., Vincent,B., Ring,S., D'Adamio,L., Shen,J., Muller,U., St George Hyslop,P. and Checler,F.
Presenilin-dependent transcriptional control of the Abeta-degrading enzyme neprilysin by intracellular domains of betaAPP and APLP
Neuron46, 541-554. PubMed Europe PubMed DOI
Pollack,S.J. and Lewis,H.
Secretase inhibitors for Alzheimer's disease: challenges of a promiscuous protease
Curr Opin Investig Drugs6, 35-47. PubMed Europe PubMed V
Prokop,S., Haass,C. and Steiner,H.
Length and overall sequence of the PEN-2 C-terminal domain determines its function in the stabilization of presenilin fragments
J Neurochem94, 57-62. PubMed Europe PubMed DOI
Qi-Takahara,Y., Morishima-Kawashima,M., Tanimura,Y., Dolios,G., Hirotani,N., Horikoshi,Y., Kametani,F., Maeda,M., Saido,T.C., Wang,R. and Ihara,Y.
Longer forms of amyloid beta protein: implications for the mechanism of intramembrane cleavage by gamma-secretase
J Neurosci25, 436-445. PubMed Europe PubMed DOI I
[YEAR:7-7-2005]Quelever,G., Kachidian,P., Melon,C., Garino,C., Laras,Y., Pietrancosta,N., Sheha,M. and Louis Kraus,J.
Enhanced delivery of gamma-secretase inhibitor DAPT into the brain via an ascorbic acid mediated strategy
Org Biomol Chem3, 2450-2457. PubMed Europe PubMed DOI I
Raemaekers,T., Esselens,C. and Annaert,W.
Presenilin 1: more than just gamma-secretase
Biochem Soc Trans33, 559-562. PubMed Europe PubMed DOI
[YEAR:1-3-2005]Ravi Keerti,A., Ashok Kumar,B., Parthasarathy,T. and Uma,V.
QSAR studies - potent benzodiazepine gamma-secretase inhibitors
Bioorg Med Chem13, 1873-1878. PubMed Europe PubMed DOI I
[YEAR:4-2-2005]Saito,S. and Araki,W.
Expression profiles of two human APH-1 genes and their roles in formation of presenilin complexes
Biochem Biophys Res Commun327, 18-22. PubMed Europe PubMed DOI
[YEAR:1-2-2005]Serneels,L., Dejaegere,T., Craessaerts,K., Horre,K., Jorissen,E., Tousseyn,T., Hebert,S., Coolen,M., Martens,G., Zwijsen,A., Annaert,W., Hartmann,D. and De Strooper,B.
Differential contribution of the three Aph1 genes to gamma-secretase activity in vivo
Proc Natl Acad Sci U S A102, 1719-1724. PubMed Europe PubMed DOI
[YEAR:12-8-2005]Shah,S., Lee,S.F., Tabuchi,K., Hao,Y.H., Yu,C., LaPlant,Q., Ball,H., Dann,C.E., III, Sudhof,T. and Yu,G.
Nicastrin functions as a gamma-secretase-substrate receptor
Cell122, 435-447. PubMed Europe PubMed DOI
[YEAR:26-7-2005]Sparey,T., Beher,D., Best,J., Biba,M., Castro,J.L., Clarke,E., Hannam,J., Harrison,T., Lewis,H., Madin,A., Shearman,M., Sohal,B., Tsou,N., Welch,C. and Wrigley,J.
Cyclic sulfamide gamma-secretase inhibitors
Bioorg Med Chem Lett15, 4212-4216. PubMed Europe PubMed DOI I
[YEAR:31-8-2005]Stromberg,K., Hansson,E.M., Laudon,H., Bergstedt,S., Naslund,J., Lundkvist,J. and Lendahl,U.
gamma-Secretase complexes containing N- and C-terminal fragments of different presenilin origin retain normal gamma-secretase activity
J Neurochem95, 880-890. PubMed Europe PubMed DOI
[YEAR:16-5-2005]Teall,M., Oakley,P., Harrison,T., Shaw,D., Kay,E., Elliott,J., Gerhard,U., Castro,J.L., Shearman,M., Ball,R.G. and Tsou,N.N.
Aryl sulfones: a new class of gamma-secretase inhibitors
Bioorg Med Chem Lett15, 2685-2688. PubMed Europe PubMed DOI I
[YEAR:16-2-2005]Urano,Y., Hayashi,I., Isoo,N., Reid,P.C., Shibasaki,Y., Noguchi,N., Tomita,T., Iwatsubo,T., Hamakubo,T. and Kodama,T.
Association of active gamma-secretase complex with lipid rafts
J Lipid Res46, 904-912. PubMed Europe PubMed DOI
[YEAR:16-6-2005]van Es,J.H., van Gijn,M.E., Riccio,O., van den Born,M., Vooijs,M., Begthel,H., Cozijnsen,M., Robine,S., Winton,D.J., Radtke,F. and Clevers,H.
Notch/gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells
Nature435, 959-963. PubMed Europe PubMed DOI
[YEAR:3-3-2005]Vidal,G.A., Naresh,A., Marrero,L. and Jones,F.E.
Presenilin-dependent gamma-secretase processing regulates multiple ERBB4/HER4 activities
J Biol Chem280, 19777-19783. PubMed Europe PubMed DOI
[YEAR:18-10-2005]Watanabe,N., Tomita,T., Sato,C., Kitamura,T., Morohashi,Y. and Iwatsubo,T.
Pen-2 is incorporated into the gamma-secretase complex through binding to transmembrane domain 4 of presenilin 1
J Biol Chem280, 41967-41975. PubMed Europe PubMed DOI
[YEAR:3-8-2005]Wen,P.H., De Gasperi,R., Sosa,M.A., Rocher,A.B., Friedrich,V.L., Jr., Hof,P.R. and Elder,G.A.
Selective expression of presenilin 1 in neural progenitor cells rescues the cerebral hemorrhages and cortical lamination defects in presenilin 1-null mutant mice
Development132, 3873-3883. PubMed Europe PubMed DOI K
[YEAR:1-6-2005]Wiley,J.C., Hudson,M., Kanning,K.C., Schecterson,L.C. and Bothwell,M.
Familial Alzheimer's disease mutations inhibit gamma-secretase-mediated liberation of beta-amyloid precursor protein carboxy-terminal fragment
J Neurochem94, 1189-1201. PubMed Europe PubMed DOI
Wong,H.K., Sakurai,T., Oyama,F., Kaneko,K., Wada,K., Miyazaki,H., Kurosawa,M., De Strooper,B., Saftig,P. and Nukina,N.
beta Subunits of voltage-gated sodium channels are novel substrates of beta-site amyloid precursor protein-cleaving enzyme (BACE1) and gamma-secretase
J Biol Chem280, 23009-23017. PubMed Europe PubMed DOI
[YEAR:21-12-2005]Wrigley,J.D., Schurov,I., Nunn,E.J., Martin,A.C., Clarke,E.E., Ellis,S., Bonnert,T.P., Shearman,M.S. and Beher,D.
Functional overexpression of gamma-secretase reveals protease-independent trafficking functions and a critical role of lipids for protease activity
J Biol Chem280, 12523-12535. PubMed Europe PubMed DOI
[YEAR:22-3-2005]Zhang,L., Lee,J., Song,L., Sun,X., Shen,J., Terracina,G. and Parker,E.M.
Characterization of the reconstituted gamma-secretase complex from Sf9 cells co-expressing presenilin 1, nicastrin, aph-1a, and pen-2
Biochemistry44, 4450-4457. PubMed Europe PubMed DOI
[YEAR:11-2-2005]Zhang,Y.W., Luo,W.J., Wang,H., Lin,P., Vetrivel,K.S., Liao,F., Li,F., Wong,P.C., Farquhar,M.G., Thinakaran,G. and Xu,H.
Nicastrin is critical for stability and trafficking but not association of other presenilin/gamma-secretase components
J Biol Chem280, 17020-17026. PubMed Europe PubMed DOI
[YEAR:24-5-2005]Zhou,S., Zhou,H., Walian,P.J. and Jap,B.K.
CD147 is a regulatory subunit of the gamma-secretase complex in Alzheimer's disease amyloid beta-peptide production
Proc Natl Acad Sci U S A102, 7499-7504. PubMed Europe PubMed DOI

2004

[YEAR:16-12-2004]Bakshi,P. and Wolfe,M.S.
Stereochemical analysis of (hydroxyethyl)urea peptidomimetic inhibitors of gamma-secretase
J Med Chem47, 6485-6489. PubMed Europe PubMed DOI I
[YEAR:1-9-2004]Beglopoulos,V., Sun,X., Saura,C.A., Lemere,C.A., Kim,R.D. and Shen,J.
Reduced beta-amyloid production and increased inflammatory responses in presenilin conditional knock-out mice
J Biol Chem279, 46907-46914. PubMed Europe PubMed DOI K
[YEAR:10-8-2004]Beher,D., Clarke,E.E., Wrigley,J.D., Martin,A.C., Nadin,A., Churcher,I. and Shearman,M.S.
Selected non-steroidal anti-inflammatory drugs and their derivatives target gamma-secretase at a novel site. Evidence for an allosteric mechanism
J Biol Chem279, 43419-43426. PubMed Europe PubMed DOI
[YEAR:20-8-2004]Bergman,A., Laudon,H., Winblad,B., Lundkvist,J. and Naslund,J.
The extreme C terminus of presenilin 1 is essential for gamma-secretase complex assembly and activity
J Biol Chem279, 45564-45572. PubMed Europe PubMed DOI
[YEAR:29-7-2004]Bihel,F., Das,C., Bowman,M.J. and Wolfe,M.S.
Discovery of a subnanomolar helical D-tridecapeptide inhibitor of gamma-secretase
J Med Chem47, 3931-3933. PubMed Europe PubMed DOI I
Carter,T.L., Verdile,G., Groth,D., Bogush,A., Thomas,S., Shen,P., Fraser,P.E., Mathews,P., Nixon,R.A., Ehrlich,M.E., Kwok,J.B., St George-Hyslop,P., Schofield,P., Li,Y., Yang,A., Martins,R.N. and Gandy,S.
Alzheimer amyloid precursor aspartyl proteinase activity in CHAPSO homogenates of Spodoptera frugiperda cells
Alzheimer Dis Assoc Disord18, 261-263. PubMed Europe PubMed E
[YEAR:25-6-2004]Cervantes,S., Saura,C.A., Pomares,E., Gonzalez-Duarte,R. and Marfany,G.
Functional implications of the presenilin dimerization: reconstitution of gamma-secretase activity by assembly of a catalytic site at the dimer interface of two catalytically inactive presenilins
J Biol Chem279, 36519-36529. PubMed Europe PubMed DOI
Dominguez,D.I., Hartmann,D. and De Strooper,B.
BACE1 and presenilin: two unusual aspartyl proteases involved in Alzheimer's disease
Neurodegener Dis1, 168-174. PubMed Europe PubMed DOI
[YEAR:21-6-2004]Edbauer,D., Kaether,C., Steiner,H. and Haass,C.
Co-expression of nicastrin and presenilin rescues a loss of function mutant of APH-1
J Biol Chem279, 37311-37315. PubMed Europe PubMed DOI
[YEAR:19-4-2004]Esler,W.P., Das,C. and Wolfe,M.S.
Probing pockets S2-S4' of the gamma-secretase active site with (hydroxyethyl)urea peptidomimetics
Bioorg Med Chem Lett14, 1935-1938. PubMed Europe PubMed DOI
[YEAR:25-5-2004]Feng,R., Wang,H., Wang,J., Shrom,D., Zeng,X. and Tsien,J.Z.
Forebrain degeneration and ventricle enlargement caused by double knockout of Alzheimer's presenilin-1 and presenilin-2
Proc Natl Acad Sci U S A101, 8162-8167. PubMed Europe PubMed DOI
[YEAR:20-1-2004]Fraering,P.C., LaVoie,M.J., Ye,W., Ostaszewski,B.L., Kimberly,W.T., Selkoe,D.J. and Wolfe,M.S.
Detergent-dependent dissociation of active gamma-secretase reveals an interaction between Pen-2 and PS1-NTF and offers a model for subunit organization within the complex
Biochemistry43, 323-333. PubMed Europe PubMed DOI
[YEAR:3-8-2004]Fraering,P.C., Ye,W., Strub,J.M., Dolios,G., LaVoie,M.J., Ostaszewski,B.L., Van Dorsselaer,A., Wang,R., Selkoe,D.J. and Wolfe,M.S.
Purification and characterization of the human gamma-secretase complex
Biochemistry43, 9774-9789. PubMed Europe PubMed DOI I
[YEAR:30-4-2004]Gu,Y., Sanjo,N., Chen,F., Hasegawa,H., Petit,A., Ruan,X., Li,W., Shier,C., Kawarai,T., Schmitt-Ulms,G., Westaway,D., St George-Hyslop,P. and Fraser,P.E.
The presenilin proteins are components of multiple membrane-bound complexes that have different biological activities
J Biol Chem279, 31329-31336. PubMed Europe PubMed DOI
[YEAR:4-8-2004]Gupta,S., Singh,R., Datta,P., Zhang,Z., Orr,C., Lu,Z., Dubois,G., Zervos,A.S., Meisler,M.H., Srinivasula,S.M., Fernandes-Alnemri,T. and Alnemri,E.S.
The C-terminal tail of presenilin regulates Omi/HtrA2 protease activity
J Biol Chem279, 45844-45854. PubMed Europe PubMed DOI
[YEAR:28-9-2004]Hansson,C.A., Frykman,S., Farmery,M.R., Tjernberg,L.O., Nilsberth,C., Pursglove,S.E., Ito,A., Winblad,B., Cowburn,R.F., Thyberg,J. and Ankarcrona,M.
Nicastrin, presenilin, APH-1, and PEN-2 form active gamma-secretase complexes in mitochondria
J Biol Chem279, 51654-51660. PubMed Europe PubMed DOI I
Harrison,T., Churcher,I. and Beher,D.
gamma-Secretase as a target for drug intervention in Alzheimer's disease
Curr Opin Drug Discov Devel7, 709-719. PubMed Europe PubMed V
[YEAR:23-6-2004]Hayashi,I., Urano,Y., Fukuda,R., Isoo,N., Kodama,T., Hamakubo,T., Tomita,T. and Iwatsubo,T.
Selective reconstitution and recovery of functional gamma-secretase complex on budded baculovirus particles
J Biol Chem279, 38040-38046. PubMed Europe PubMed DOI
[YEAR:8-12-2004]Kaether,C., Capell,A., Edbauer,D., Winkler,E., Novak,B., Steiner,H. and Haass,C.
The presenilin C-terminus is required for ER-retention, nicastrin-binding and gamma-secretase activity
EMBO J23, 4738-4748. PubMed Europe PubMed DOI
Kilb,W., Hartmann,D., Saftig,P. and Luhmann,H.J.
Altered morphological and electrophysiological properties of Cajal-Retzius cells in cerebral cortex of embryonic presenilin-1 knockout mice
Eur J Neurosci20, 2749-2756. PubMed Europe PubMed DOI K
[YEAR:29-9-2004]Kim,S.H., Yin,Y.I., Li,Y.M. and Sisodia,S.S.
Evidence that assembly of an active gamma-secretase complex occurs in the early compartments of the secretory pathway
J Biol Chem279, 48615-48619. PubMed Europe PubMed DOI
[YEAR:25-5-2004]Knappenberger,K.S., Tian,G., Ye,X., Sobotka-Briner,C., Ghanekar,S.V., Greenberg,B.D. and Scott,C.W.
Mechanism of gamma-secretase cleavage activation: is gamma-secretase regulated through autoinhibition involving the presenilin-1 exon 9 loop?
Biochemistry43, 6208-6218. PubMed Europe PubMed DOI I
Kopan,R. and Ilagan,M.X.
Gamma-secretase: proteasome of the membrane?
Nat Rev Mol Cell Biol5, 499-504. PubMed Europe PubMed DOI
Landman,N. and Kim,T.W.
Got RIP? Presenilin-dependent intramembrane proteolysis in growth factor receptor signaling
Cytokine Growth Factor Rev15, 337-351. PubMed Europe PubMed DOI
[YEAR:12-1-2004]Lanz,T.A., Hosley,J.D., Adams,W.J. and Merchant,K.M.
Studies of Abeta pharmacodynamics in the brain, cerebrospinal fluid, and plasma in young (plaque-free) Tg2576 mice using the gamma-secretase inhibitor N2-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-N1-[(7S)-5-methyl-6-oxo -6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-L-alaninamide (LY-411575)
J Pharmacol Exp Ther309, 49-55. PubMed Europe PubMed DOI I
Larbig,G., Zall,A. and Schmidt,B.
Inhibitors designed for presenilin 1 by means of aspartic acid activation
Helv Chim Acta87, 2334-2340. I
[YEAR:29-3-2004]Laudon,H., Karlstrom,H., Mathews,P.M., Farmery,M.R., Gandy,S.E., Lundkvist,J., Lendahl,U. and Naslund,J.
Functional domains in presenilin 1: the Tyr-288 residue controls gamma-secretase activity and endoproteolysis
J Biol Chem279, 23925-23932. PubMed Europe PubMed DOI
[YEAR:6-2-2004]Lee,S.F., Shah,S., Yu,C., Wigley,W.C., Li,H., Lim,M., Pedersen,K., Han,W., Thomas,P., Lundkvist,J., Hao,Y.H. and Yu,G.
A conserved GXXXG motif in APH-1 is critical for assembly and activity of the gamma-secretase complex
J Biol Chem279, 4144-4152. PubMed Europe PubMed DOI
Lleo,A., Berezovska,O., Herl,L., Raju,S., Deng,A., Bacskai,B.J., Frosch,M.P., Irizarry,M. and Hyman,B.T.
Nonsteroidal anti-inflammatory drugs lower Abeta42 and change presenilin 1 conformation
Nat Med10, 1065-1066. PubMed Europe PubMed DOI
Menendez,M.
Pathological and clinical heterogeneity of presenilin 1 gene mutations
J Alzheimers Dis6, 475-482. PubMed Europe PubMed M V
Pan,Y., Lin,M.H., Tian,X., Cheng,H.T., Gridley,T., Shen,J. and Kopan,R.
gamma-Secretase functions through Notch signaling to maintain skin appendages but is not required for their patterning or initial morphogenesis
Dev Cell7, 731-743. PubMed Europe PubMed DOI
[YEAR:18-11-2004]Popescu,B.O., Cedazo-Minguez,A., Benedikz,E., Nishimura,T., Winblad,B., Ankarcrona,M. and Cowburn,R.F.
gamma-Secretase activity of presenilin 1 regulates acetylcholine muscarinic receptor-mediated signal transduction
J Biol Chem279, 6455-6464. PubMed Europe PubMed DOI I
[YEAR:5-7-2004]Prasad,C.V., Vig,S., Smith,D.W., Gao,Q., Polson,C.T., Corsa,J.A., Guss,V.L., Loo,A., Barten,D.M., Zheng,M., Felsenstein,K.M. and Roberts,S.B.
2,3-Benzodiazepin-1,4-diones as peptidomimetic inhibitors of gamma-secretase
Bioorg Med Chem Lett14, 3535-3538. PubMed Europe PubMed DOI I
[YEAR:19-4-2004]Prasad,C.V., Wallace,O.B., Noonan,J.W., Sloan,C.P., Lau,W., Vig,S., Parker,M.F., Smith,D.W., Hansel,S.B., Polson,C.T., Barten,D.M., Felsenstein,K.M. and Roberts,S.B.
Hydroxytriamides as potent gamma-secretase inhibitors
Bioorg Med Chem Lett14, 1917-1921. PubMed Europe PubMed DOI I
[YEAR:23-3-2004]Prokop,S., Shirotani,K., Edbauer,D., Haass,C. and Steiner,H.
Requirement of PEN-2 for stabilization of the presenilin N-/C-terminal fragment heterodimer within the gamma-secretase complex
J Biol Chem279, 23255-23261. PubMed Europe PubMed DOI
[YEAR:8-4-2004]Saura,C.A., Choi,S.Y., Beglopoulos,V., Malkani,S., Zhang,D., Shankaranarayana Rao,B.S., Chattarji,S., Kelleher,R.J., III, Kandel,E.R., Duff,K., Kirkwood,A. and Shen,J.
Loss of presenilin function causes impairments of memory and synaptic plasticity followed by age-dependent neurodegeneration
Neuron42, 23-36. PubMed Europe PubMed DOI K
[YEAR:5-10-2004]Scheper,W., Zwart,R. and Baas,F.
Alternative splicing in the N-terminus of Alzheimer's presenilin 1
Neurogenetics5, 223-227. PubMed Europe PubMed DOI R
Shiraishi,H., Sai,X., Wang,H.Q., Maeda,Y., Kurono,Y., Nishimura,M., Yanagisawa,K. and Komano,H.
PEN-2 enhances gamma-cleavage after presenilin heterodimer formation
J Neurochem90, 1402-1413. PubMed Europe PubMed DOI
Siman,R. and Salidas,S.
Gamma-secretase subunit composition and distribution in the presenilin wild-type and mutant mouse brain
Neuroscience129, 615-628. PubMed Europe PubMed DOI
Steiner,H.
Uncovering gamma-secretase
Curr Alzheimer Res1, 175-181. PubMed Europe PubMed V
Tomita,T. and Iwatsubo,T.
The inhibition of gamma-secretase as a therapeutic approach to Alzheimer's disease
Drug News Perspect17, 321-325. PubMed Europe PubMed DOI I
[YEAR:2-3-2004]Verdile,G., Groth,D., Mathews,P.M., St George-Hyslop,P., Fraser,P.E., Ramabhadran,T.V., Kwok,J.B., Schofield,P.R., Carter,T., Gandy,S. and Martins,R.N.
Baculoviruses expressing the human familial Alzheimer's disease presenilin 1 mutation lacking exon 9 increase levels of an amyloid beta-like protein in Sf9 cells
Mol Psychiatry9, 594-602. PubMed Europe PubMed DOI
[YEAR:22-10-2004]Vetrivel,K.S., Cheng,H., Lin,W., Sakurai,T., Li,T., Nukina,N., Wong,P.C., Xu,H. and Thinakaran,G.
Association of gamma-secretase with lipid rafts in post-Golgi and endosome membranes
J Biol Chem279, 44945-44954. PubMed Europe PubMed DOI
[YEAR:4-10-2004]Vooijs,M., Schroeter,E.H., Pan,Y., Blandford,M. and Kopan,R.
Ectodomain shedding and intramembrane cleavage of mammalian notch proteins is not regulated through oligomerization
J Biol Chem279, 50864-50873. PubMed Europe PubMed DOI
Wang,J., Brunkan,A.L., Hecimovic,S., Walker,E. and Goate,A.
Conserved "PAL" sequence in presenilins is essential for gamma-secretase activity, but not required for formation or stabilization of gamma-secretase complexes
Neurobiol Dis15, 654-666. PubMed Europe PubMed DOI
[YEAR:23-11-2004]Wen,P.H., De Gasperi,R., Gama Sosa,M.A. and Elder,G.A.
Neural progenitor cells do not differentiate prematurely in presenilin-1 null mutant mice
Neurosci Lett371, 249-254. PubMed Europe PubMed DOI K
Wolfe,M.S.
Presenilins
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[YEAR:6-1-2004]Wong,G.T., Manfra,D., Poulet,F.M., Zhang,Q., Josien,H., Bara,T., Engstrom,L., Pinzon-Ortiz,M., Fine,J.S., Lee,H.J., Zhang,L., Higgins,G.A. and Parker,E.M.
Chronic treatment with the gamma-secretase inhibitor LY-411,575 inhibits beta-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation
J Biol Chem279, 12876-12882. PubMed Europe PubMed DOI I
Wrigley,J.D., Nunn,E.J., Nyabi,O., Clarke,E.E., Hunt,P., Nadin,A., De Strooper,B., Shearman,M.S. and Beher,D.
Conserved residues within the putative active site of gamma-secretase differentially influence enzyme activity and inhibitor binding
J Neurochem90, 1312-1320. PubMed Europe PubMed DOI
[YEAR:13-10-2004]Zhao,G., Mao,G., Tan,J., Dong,Y., Cui,M.Z., Kim,S.H. and Xu,X.
Identification of a new presenilin-dependent zeta-cleavage site within the transmembrane domain of amyloid precursor protein
J Biol Chem279, 50647-50650. PubMed Europe PubMed DOI

2003

Baulac,S., LaVoie,M.J., Kimberly,W.T., Strahle,J., Wolfe,M.S., Selkoe,D.J. and Xia,W.
Functional gamma-secretase complex assembly in Golgi/trans-Golgi network: interactions among presenilin, nicastrin, Aph1, Pen-2, and gamma-secretase substrates
Neurobiol Dis14, 194-204. PubMed Europe PubMed DOI
[YEAR:15-7-2003]Beher,D., Fricker,M., Nadin,A., Clarke,E.E., Wrigley,J.D., Li,Y.M., Culvenor,J.G., Masters,C.L., Harrison,T. and Shearman,M.S.
In vitro characterization of the presenilin-dependent gamma-secretase complex using a novel affinity ligand
Biochemistry42, 8133-8142. PubMed Europe PubMed DOI
[YEAR:26-12-2003]Capell,A., Kaether,C., Edbauer,D., Shirotani,K., Merkl,S., Steiner,H. and Haass,C.
Nicastrin interacts with gamma-secretase complex components via the N-terminal part of its transmembrane domain
J Biol Chem278, 52519-52523. PubMed Europe PubMed DOI
[YEAR:10-4-2003]De Strooper,B.
Aph-1, Pen-2, and nicastrin with presenilin generate an active gamma-secretase complex
Neuron38, 9-12. PubMed Europe PubMed DOI
Edbauer,D., Winkler,E., Regula,J.T., Pesold,B., Steiner,H. and Haass,C.
Reconstitution of gamma-secretase activity
Nat Cell Biol5, 486-488. PubMed Europe PubMed DOI
[YEAR:11-4-2003]Grimm,H.S., Beher,D., Lichtenthaler,S.F., Shearman,M.S., Beyreuther,K. and Hartmann,T.
gamma-Secretase cleavage site specificity differs for intracellular and secretory amyloid beta
J Biol Chem278, 13077-13085. PubMed Europe PubMed DOI
[YEAR:31-1-2003]Hebert,S.S., Godin,C., Tomiyama,T., Mori,H. and Levesque,G.
Dimerization of presenilin-1 in vivo: suggestion of novel regulatory mechanisms leading to higher order complexes
Biochem Biophys Res Commun301, 119-126. PubMed Europe PubMed DOI M
Ikeuchi,T. and Sisodia,S.S.
The Notch ligands, Delta1 and Jagged2, are substrates for presenilin-dependent "gamma-secretase" cleavage
J Biol Chem278, 7751-7754. PubMed Europe PubMed DOI P
[YEAR:28-2-2003]Ikeuchi,T., Dolios,G., Kim,S.H., Wang,R. and Sisodia,S.S.
Familial Alzheimer disease-linked presenilin 1 variants enhance production of both Abeta 1-40 and Abeta 1-42 peptides that are only partially sensitive to a potent aspartyl protease transition state inhibitor of "gamma-secretase"
J Biol Chem278, 7010-7018. PubMed Europe PubMed DOI I
[YEAR:14-1-2003]Kimberly,W.T., Esler,W.P., Ye,W., Ostaszewski,B.L., Gao,J., Diehl,T., Selkoe,D.J. and Wolfe,M.S.
Notch and the amyloid precursor protein are cleaved by similar gamma-secretase(s)
Biochemistry42, 137-144. PubMed Europe PubMed DOI
[YEAR:27-5-2003]Kimberly,W.T., LaVoie,M.J., Ostaszewski,B.L., Ye,W., Wolfe,M.S. and Selkoe,D.J.
Gamma-secretase is a membrane protein complex comprised of presenilin, nicastrin, Aph-1, and Pen-2
Proc Natl Acad Sci U S A100, 6382-6387. PubMed Europe PubMed DOI
[YEAR:9-5-2003]Kornilova,A.Y., Das,C. and Wolfe,M.S.
Differential effects of inhibitors on the gamma-secretase complex. Mechanistic implications
J Biol Chem278, 16470-16473. PubMed Europe PubMed DOI I
[YEAR:20-6-2003]Lai,M.T., Chen,E., Crouthamel,M.C., DiMuzio-Mower,J., Xu,M., Huang,Q., Price,E., Register,R.B., Shi,X.P., Donoviel,D.B., Bernstein,A., Hazuda,D., Gardell,S.J. and Li,Y.M.
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Presenilin-dependent gamma-secretase activity mediates the intramembranous cleavage of CD44
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Presenilin-1, nicastrin, amyloid precursor protein, and gamma-secretase activity are co-localized in the lysosomal membrane
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JLK isocoumarin inhibitors: selective gamma-secretase inhibitors that do not interfere with notch pathway in vitro or in vivo
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A presenilin dimer at the core of the gamma-secretase enzyme: insights from parallel analysis of Notch 1 and APP proteolysis
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Selkoe,D. and Kopan,R.
Notch and Presenilin: regulated intramembrane proteolysis links development and degeneration
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The Notch ligand Delta1 is sequentially cleaved by an ADAM protease and gamma-secretase
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The mechanism of gamma-secretase: multiple inhibitor binding sites for transition state analogs and small molecule inhibitors
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[YEAR:15-7-2003]Uemura,K., Kitagawa,N., Kohno,R., Kuzuya,A., Kageyama,T., Shibasaki,H. and Shimohama,S.
Presenilin 1 mediates retinoic acid-induced differentiation of SH-SY5Y cells through facilitation of Wnt signaling
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2002

Beher,D. and Shearman,M.S.
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Activity-dependent isolation of the presenilin-gamma-secretase complex reveals nicastrin and a gamma substrate
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Goutte,C., Tsunozaki,M., Hale,V.A. and Priess,J.R.
APH-1 is a multipass membrane protein essential for the Notch signaling pathway in Caenorhabditis elegans embryos
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Alzheimer disease gamma-secretase: a complex story of GxGD-type presenilin proteases
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Presenilin-dependent intramembrane proteolysis of CD44 leads to the liberation of its intracellular domain and the secretion of an Abeta-like peptide
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Mammalian APH-1 interacts with presenilin and nicastrin and is required for intramembrane proteolysis of amyloid-beta precursor protein and Notch
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Presenilin 1 is required for maturation and cell surface accumulation of nicastrin
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A presenilin-1/gamma-secretase cleavage releases the E-cadherin intracellular domain and regulates disassembly of adherens junctions
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FAD-linked mutations in presenilin 1 alter the length of Abeta peptides derived from betaAPP transmembrane domain mutants
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Presenilins mediate a dual intramembranous gamma-secretase cleavage of Notch-1
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Pitsi,D., Kienlen-Campard,P. and Octave,J.N.
Failure of the interaction between presenilin 1 and the substrate of gamma-secretase to produce Abeta in insect cells
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Normal brain development in PS1 hypomorphic mice with markedly reduced gamma-secretase cleavage of betaAPP
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PEN-2 is an integral component of the gamma-secretase complex required for coordinated expression of presenilin and nicastrin
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The mechanism of gamma-secretase activities through high molecular weight complex formation of presenilins is conserved in Drosophila melanogaster and mammals
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Linear non-competitive inhibition of solubilized human gamma-secretase by pepstatin A methylester, L685458, sulfonamides, and benzodiazepines
J Biol Chem277, 31499-31505. PubMed Europe PubMed DOI I
Wolfe,M.S.
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The aspartate-257 of presenilin 1 is indispensable for mouse development and production of beta-amyloid peptides through beta-catenin-independent mechanisms
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Xu,M., Lai,M.T., Huang,Q., DiMuzio-Mower,J., Castro,J.L., Harrison,T., Nadin,A., Neduvelil,J.G., Shearman,M.S., Shafer,J.A., Gardell,S.J. and Li,Y.M.
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2001

[YEAR:30-11-2001]Beher,D., Wrigley,J.D., Nadin,A., Evin,G., Masters,C.L., Harrison,T., Castro,J.L. and Shearman,M.S.
Pharmacological knock-down of the presenilin 1 heterodimer by a novel gamma-secretase inhibitor: implications for presenilin biology
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Notch1 and amyloid precursor protein are competitive substrates for presenilin1-dependent gamma-secretase cleavage
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Homodimerization of presenilin N-terminal fragments is affected by mutations linked to Alzheimer's disease
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The discrepancy between presenilin subcellular localization and gamma-secretase processing of amyloid precursor protein
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Presenilin-dependent gamma-secretase activity modulates thymocyte development
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Dominguez,D.I., De Strooper,B. and Annaert,W.
Secretases as therapeutic targets for the treatment of Alzheimer's disease
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Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain
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Aspartyl protease inhibitor pepstatin binds to the presenilins of Alzheimer's disease
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Fortini,M.E.
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Presenilin 1 mutations increase amyloid precursor protein production and proteolysis in Xenopus laevis oocytes
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Effect of PS1 deficiency and an APP gamma-secretase inhibitor on Notch1 signaling in primary mammalian neurons
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Human wild presenilin-1 mimics the effect of the mutant presenilin-1 on the processing of Alzheimer's amyloid precursor protein in PC12D cells
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Koizumi,K., Nakajima,M., Yuasa,S., Saga,Y., Sakai,T., Kuriyama,T., Shirasawa,T. and Koseki,H.
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PS1 N- and C-terminal fragments form a complex that functions in APP processing and Notch signaling
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Cases of Alzheimer's disease due to deletion of exon 9 of the presenilin-1 gene show an unusual but characteristic beta-amyloid pathology known as 'cotton wool' plaques
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Mann,D.M., Pickering-Brown,S.M., Takeuchi,A. and Iwatsubo,T.
Amyloid angiopathy and variability in amyloid beta deposition is determined by mutation position in presenilin-1-linked Alzheimer's disease
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PAMP and PARL, two novel putative metalloproteases interacting with the COOH-terminus of Presenilin-1 and -2
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New protease inhibitors prevent gamma-secretase-mediated production of Abeta40/42 without affecting Notch cleavage
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Sastre,M., Steiner,H., Fuchs,K., Capell,A., Multhaup,G., Condron,M.M., Teplow,D.B. and Haass,C.
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Presenilin, Notch, and the genesis and treatment of Alzheimer's disease
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Soriano,S., Kang,D.E., Fu,M., Pestell,R., Chevallier,N., Zheng,H. and Koo,E.H.
Presenilin 1 negatively regulates beta-catenin/T cell factor/lymphoid enhancer factor-1 signaling independently of beta-amyloid precursor protein and Notch processing
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A pathogenic presenilin-1 deletion causes abberrant Abeta42 production in the absence of congophilic amyloid plaques
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The first proline of PALP motif at the C terminus of presenilins is obligatory for stabilization, complex formation, and gamma-secretase activities of presenilins
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Wolfe,M.S.
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Secretase targets for Alzheimer's disease: identification and therapeutic potential
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Wolfe,M.S.
Presenilin and gamma-secretase: structure meets function
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The role of presenilins in gamma-secretase activity
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Loss of presenilin 1 is associated with enhanced beta-catenin signaling and skin tumorigenesis
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Characterization of a presenilin-mediated amyloid precursor protein carboxyl-terminal fragment gamma. Evidence for distinct mechanisms involved in gamma -secretase processing of the APP and Notch1 transmembrane domains
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Zhang,L., Song,L., Terracina,G., Liu,Y., Pramanik,B. and Parker,E.
Biochemical characterization of the gamma-secretase activity that produces beta-amyloid peptides
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2000

Berezovska,O., Jack,C., McLean,P., Aster,J.C., Hicks,C., Xia,W., Wolfe,M.S., Kimberly,W.T., Weinmaster,G., Selkoe,D.J. and Hyman,B.T.
Aspartate mutations in presenilin and gamma-secretase inhibitors both impair Notch1 proteolysis and nuclear translocation with relative preservation of Notch1 signaling
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1999

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1998

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1997

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1996

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1995

Campion,D., Flaman,J.M., Brice,A., Hannequin,D., Dubois,B., Martin,C., Moreau,V., Charbonnier,F., Didierjean,O. and Tardieu,S.
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