Microarray expression analysis reveals genetic pathways implicated in C621 synphilin-1-mediated toxicity.
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.
Bonin
M
M
Department of Medical Genetics, Microarray Facility, University of Tübingen, Tübingen, Germany.
Marx
F P
FP
Kautzmann
S
S
Riess
O
O
Krüger
R
R
D001120:Arginine / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002461:Cell Line, Transformed; D003545:Cysteine / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D015398:Signal Transduction / Q000235:genetics*; D014162:Transfection / Q000379:methods; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; C118958:SNCAIP protein, human; D016212:Transforming Growth Factor beta; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D001120:Arginine; D003545:Cysteine