No document available.
Keywords :
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
Abstract :
[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.
Scopus citations®
without self-citations
2