Mechanistic models describing neurodegenerative disease processes

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Model space in neurodegeneration - model landscape map. This cellular and molecular process diagram of neurodegeneration was created by integrating the mechanisms described in 89 neurodegenerative disease models published in the literature. It is an abstract representation of the processes involved, i.e. only important mechanisms of each process are shown for better visualisation. Boundaries of subcellular organelles are represented as solid lines, cell boundaries as thick solid lines and the blood-brain barrier as thick dotted lines. The 15 biological processes associated with ND that the models describe are in capital bold red font. The models falling under each of these processes are displayed as numbers and hyperlinked to the original publication or if the models exist in BioModels it is linked to model page in BioModels. Models involving more than one process are over-lined. The density of distribution of models in each process is illustrated as colour gradient (gradient definition is provided in the figure).

image/svg+xmlAstrocyte Activated Microglia Blood - Brain Barrier Extracellular Space Neuron Autophagosome Lysosome Mitochondrion Mitochondrion Cell membrane Microtubule ETC ER ETC Proteasome Nucleus DNA RNA Dam DNA Microtubule Quiescient Microglia ApoE ROS APP α-Syn Secretases Presinilins Micelle Toxic protein Antibodies O 2 LAC ACh ACh DA DA Hormones & Neurotransmitters Cortisol ApoE Cholesterol ROS ROS Ion Channels ∆V K + Na + GLC PYR LAC GLC PYR LAC LAC ATP ADP Cr PCr ATP ADP Cr PCr Reaction Activation Inhibition GSH Apoptosis GSH GSSG Fatty Acid Amino Acid Na + Ca 2+ LAC GLC GLC DA, ACh, Cortisol, Cholesterol and so Acetyl-CoA Tau Tau Tangles Caspases 1-3 models 3-15 models + 15 models Soluble Aβ Misfolded Aβ Aβ Plaques Amyloid Aggregates GSK3β p53 Mdm2 Protein Fibrils Lewy Body Fibrils Ub Ub Ub Tau P P P Chaperones Ca 2+ Sugar Cholesterol Cholesterol Tyr CO 2 O 2 CO 2 Cys Gly Glu Chaperones ROS ROS MICROTUBULE-BASED TRANSPORT 36, 38 ENERGY METABOLISM 4, 5, 6, 9, 15, 17 41, 59, 76, 84 APP BREAKDOWN 1, 10, 22, 26, 27, 34 37, 39, 40, 41, 42, 43, 44, 56, 77, 81, 87 BBB TRANSPORT 10, 22, 37, 41, 71 PROTEIN DEGRADATION 13, 17, 39, 57, 63, 64, 65, 72, 76, 78, 83 FIBRIL ORGANIZATION 2, 7, 8, 10, 12, 13, 16, 17, 18, 19, 20, 22, 25, 33, 35, 39, 40, 41, 42, 45, 51, 52, 54, 55, 57, 58, 61, 62, 63, 64, 65, 66, 67, 68, 71 72, 76, 78, 79, 80, 83 86 TRANSMISSION 3, 11, 13, 21, 23, 26, 27, 28, 30, 31, 41, 53, 60, 70, 74, 75, 76 INTERCELLULAR SIGNALING 24, 42, 69 SYNAPTIC ION HOMEOSTASIS 18, 21, 23, 28, 30, 84, 86 INFLAMMATORY RESPONSE 24, 25, 41, 42, 49, 68, 69 APOPTOSIS 13, 14, 29, 42, 46, 47, 48, 66, 68, 69, 83 OXIDATIVE STRESS 9, 13, 16, 17, 25, 32, 46, 47, 48, 65, 66, 68, 70, 72, 73, 76, 83, 85 TAUOPATHY 18, 38, 65, 68, 89 PROTEIN REFOLDING 62, 66 GENETICS 42, 50, 82

A review of mechanistic models on neurodegenerative disease processes was published in CPT:PSP.

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