Identification of gene expression changes in transgenic C. elegans overexpressing human alpha-synuclein.

Abstract:

:Alpha-synuclein containing cellular inclusions are a hallmark of Parkinson Disease, Lewy Body Dementia, and Multiple System Atrophy. A genome wide expression screen was performed in C. elegans overexpressing both wild-type and A53T human alpha-synuclein. 433 genes were up- and 67 genes down-regulated by statistical and fold change (> or <2) criteria. Gene ontology (GO) categories within the regulated gene lists indicated over-representation of development and reproduction, mitochondria, catalytic activity, and histone groups. Seven genes (pdr-1, ubc-7, pas-5, pas-7, pbs-4, RPT2, PSMD9) with function in the ubiquitin-proteasome system and 35 mitochondrial function genes were up-regulated. Nine genes that form histones H1, H2B, and H4 were down-regulated. These results demonstrate the effects of alpha-synuclein on proteasome and mitochondrial complex gene expression and provide further support for the role of these complexes in mediating neurotoxicity. The results also indicate an effect on nuclear protein genes that suggests a potential new avenue for investigation.

journal_name

Neurobiol Dis

journal_title

Neurobiology of disease

authors

Vartiainen S,Pehkonen P,Lakso M,Nass R,Wong G

doi

10.1016/j.nbd.2005.12.021

subject

Has Abstract

pub_date

2006-06-01 00:00:00

pages

477-86

issue

3

eissn

0969-9961

issn

1095-953X

pii

S0969-9961(05)00344-X

journal_volume

22

pub_type

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