Reference : Microarray expression analysis reveals genetic pathways implicated in C621 synphilin-...
Scientific journals : Article
Life sciences : Genetics & genetic processes
http://hdl.handle.net/10993/17160
Microarray expression analysis reveals genetic pathways implicated in C621 synphilin-1-mediated toxicity.
English
Bonin, M. [> >]
Marx, F. P. [> >]
Kautzmann, S. [> >]
Riess, O. [> >]
Krüger, Rejko mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit]
2008
Journal of neural transmission (Vienna, Austria : 1996)
115
7
941-58
Yes (verified by ORBilu)
0300-9564
Austria
[en] Arginine/genetics ; Carrier Proteins/genetics ; Cell Line, Transformed ; Cysteine/genetics ; Gene Expression Regulation/genetics ; Green Fluorescent Proteins/genetics/metabolism ; Humans ; Mutation/genetics ; Nerve Tissue Proteins/genetics ; Oligonucleotide Array Sequence Analysis/methods ; Signal Transduction/genetics ; Transfection/methods ; Transforming Growth Factor beta/genetics/metabolism
[en] Synphilin-1 has been linked to Parkinson's disease (PD) based on its role as an alpha-synuclein (PARK1) and Parkin (PARK2) interacting protein and its presence in lewy bodies in brains of PD patients. We recently identified a R621C mutation in the synphilin-1 gene in German PD patients. Functional analyses revealed that mutant synphilin-1 increases cellular stress, however, the involved molecular signalling pathways are currently unknown. Using microarray based gene expression analysis of dopaminergic SH-SY5Y cells overexpressing wild type or R621C mutant synphilin-1 we investigated differentially regulated genes and signalling networks using the Ingenuity Pathways Analysis tool. We show specific effects of C621 mutant synphilin-1 on gene expression that correlate with its role as a susceptibility factor in PD. The most significantly regulated signalling network was defined by the tumor growth factor beta 1 (TGF-beta1) suggesting an involvement of synphilin-1 in TGF-beta mediated signalling pathways modulating the cellular stress response.
Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group)
http://hdl.handle.net/10993/17160
10.1007/s00702-008-0031-x

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