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

M. Bonin, F. P. Marx, S. Kautzmann, O. Riess, R. Krüger*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)


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 languageEnglish
Pages (from-to)941-958
Number of pages18
JournalJournal of Neural Transmission
Issue number7
Publication statusPublished - Jul 2008
Externally publishedYes


  • Microarray analysis
  • Neurodegeneration
  • Parkinson's disease
  • Synphilin-1
  • Tumor growth factor beta


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