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.
Original language | English |
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Pages (from-to) | 941-958 |
Number of pages | 18 |
Journal | Journal of Neural Transmission |
Volume | 115 |
Issue number | 7 |
DOIs | |
Publication status | Published - Jul 2008 |
Externally published | Yes |
Keywords
- Microarray analysis
- Neurodegeneration
- Parkinson's disease
- Synphilin-1
- Tumor growth factor beta