Abstract
Dysfunction of proteasomal protein degradation is involved in neurodegeneration in Parkinson's disease (PD). Recently we identified the regulatory proteasomal subunit S6 ATPase as a novel interactor of synphilin-1, which is a substrate of the ubiquitin-ligase Parkin (PARK2) and an interacting protein of alpha-synuclein (PARK1). To further investigate a potential role in the pathogenesis of PD, we performed a detailed mutation analysis of the S6 ATPase gene in a large sample of 486 German sporadic and familial PD patients. Direct sequencing revealed two novel intronic variants. An insertion/deletion variant in intron 5 of the S6 ATPase gene was more frequent in patients compared to controls. Moreover, this variant was significantly more frequent in early-onset compared to late-onset PD patients. The identification of a genetic link between a regulatory proteasomal subunit and PD further underscores the relevance of disturbed protein degradation in PD.
Original language | English |
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Pages (from-to) | 1141-1148 |
Number of pages | 8 |
Journal | Journal of Neural Transmission |
Volume | 115 |
Issue number | 8 |
DOIs | |
Publication status | Published - Aug 2008 |
Externally published | Yes |
Keywords
- Neurodegeneration
- Parkinson's disease
- Proteasome
- S6 ATPase
- Ubiquitin