A comprehensive genetic study of the proteasomal subunit S6 ATPase in German Parkinson's disease patients

Claudia Wahl, Sabine Kautzmann, Guido Krebiehl, Karsten Strauss, Dirk Woitalla, Thomas Müller, Peter Bauer, Olaf Riess, Rejko Krüger*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

17 Citations (Scopus)

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 languageEnglish
Pages (from-to)1141-1148
Number of pages8
JournalJournal of Neural Transmission
Volume115
Issue number8
DOIs
Publication statusPublished - Aug 2008
Externally publishedYes

Keywords

  • Neurodegeneration
  • Parkinson's disease
  • Proteasome
  • S6 ATPase
  • Ubiquitin

Fingerprint

Dive into the research topics of 'A comprehensive genetic study of the proteasomal subunit S6 ATPase in German Parkinson's disease patients'. Together they form a unique fingerprint.

Cite this