title: A comprehensive genetic study of the proteasomal subunit S6 ATPase in German Parkinson's disease patients.
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.
authors.affiliation: Laboratory of Functional Neurogenomics, Center of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Hoppe-Seyler-Str. 3, 72076, Tubingen, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Wahl
authors.forename: Sabine
authors.initials: S
authors.lastname: Kautzmann
authors.forename: Guido
authors.initials: G
authors.lastname: Krebiehl
authors.forename: Karsten
authors.initials: K
authors.lastname: Strauss
authors.forename: Dirk
authors.initials: D
authors.lastname: Woitalla
authors.forename: Thomas
authors.initials: T
authors.lastname: Müller
authors.forename: Peter
authors.initials: P
authors.lastname: Bauer
authors.forename: Olaf
authors.initials: O
authors.lastname: Riess
authors.forename: Rejko
authors.initials: R
authors.lastname: Krüger
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000235:genetics*; D000368:Aged; D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D010300:Parkinson Disease / Q000453:epidemiology* / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D046988:Proteasome Endopeptidase Complex / Q000235:genetics*; D011489:Protein Denaturation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002352:Carrier Proteins; D018076:DNA, Complementary; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C118958:SNCAIP protein, human; C088863:PSMC4 protein, human; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities