A comprehensive genetic study of the proteasomal subunit S6 ATPase in German Parkinson's disease patients
| Autor: | Sabine Kautzmann, Olaf Riess, Peter Bauer, Guido Krebiehl, Claudia Wahl, Dirk Woitalla, Karsten M. Strauss, Rejko Krüger, Thomas Müller |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Proteasome Endopeptidase Complex Protein Denaturation DNA Complementary Genotype ATPase Protein subunit DNA Mutational Analysis Nerve Tissue Proteins Protein degradation Parkin Ubiquitin Germany medicine Humans RNA Messenger Biological Psychiatry Alleles Chromatography High Pressure Liquid Aged Genetics Adenosine Triphosphatases biology Reverse Transcriptase Polymerase Chain Reaction ATPase Gene Neurodegeneration Parkinson Disease Middle Aged medicine.disease Molecular biology Introns Psychiatry and Mental health Neurology Proteasome biology.protein ATPases Associated with Diverse Cellular Activities Female Neurology (clinical) Carrier Proteins Polymorphism Restriction Fragment Length |
| Zdroj: | Journal of neural transmission (Vienna, Austria : 1996). 115(8) |
| ISSN: | 0300-9564 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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