Microarray expression analysis reveals genetic pathways implicated in C621 synphilin-1-mediated toxicity

Abstract

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.

DOI: 10.1007/s00702-008-0031-x

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@article{Bonin2008MicroarrayEA, title={Microarray expression analysis reveals genetic pathways implicated in C621 synphilin-1-mediated toxicity}, author={Michael Bonin and Frank P Marx and Sabine Kautzmann and Olaf Riess and Rejko Krueger}, journal={Journal of Neural Transmission}, year={2008}, volume={115}, pages={941-958} }