E-MEXP-389 - Transcription profiling of generic impact of protein aggregation (aggregation of proteins not associated with neurodegenerative disease) on gene expression in human cultured cells
Submitted on 13 July 2005, released on 20 July 2005, last updated on 10 June 2011
In this study the generic impact of protein aggregation (aggregation of proteins not associated with neurodegenerative disease) on gene expression in cultured cells was investigated by DNA microarray technology. The survey of gene expression showed that the Hsp40, Hsp70 and Hsp105 genes, all of which have documented aggregation suppression activity, were up-regulated. Unexpectedly, the survey also showed increased expression of the MEK5 gene with concomitant silencing of the MEK3 gene. The expression pattern of MEK5 at the mRNA and protein levels aligns with the kinetics of aggregate formation and dissolution. Cell viability was unaffected by protein aggregates. These findings are of particular importance for chronic neurodegenerative diseases where the intraneuronal accumulation of aggregate-prone proteins are a major characteristic of the diseases. The identification of changes in MEK5 gene expression have been observed in Alzheimer-related diseases which provides new diagnostic and therapeutic avenues in these diseases. The molecular neuropathological findings would not have occurred without the generic microarray analyses.
transcription profiling by array, genetic modification, time series
Roland J Mayer <John.Mayer@Nottingham.ac.uk>, Aristotelis C Dimakopoulos, Chris Harris, Chris Jones, James Lowe, Lianne Finnerty, Maureen Mee, Neil Hand, Robert Layfield, Tim Soane