How do Parkin mutations result in neurodegeneration?
The gene product responsible for autosomal recessive juvenile Parkinsonism, Parkin, has been observed to have ubiquitin ligase activity. This finding has changed the direction of studies on Parkinson's disease by suggesting that abnormal protein turnover might be involved in its pathogenesis. A number of potentially neurotoxic Parkin-specific substrates have been identified. Further investigation of Parkin knockout mice will hopefully provide new evidence in the search for Parkin's substrates and further clarify their role in Parkinson's disease.
Imai
Yuzuru
Y
Motor System Neurodegeneration, RIKEN Brain Science Institute (BSI), Saitama 351-0198, Japan.
Takahashi
Ryosuke
R
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009410:Nerve Degeneration / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D051843:Synucleins; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000172:deficiency / Q000235:genetics*
D009419:Nerve Tissue Proteins; D051843:Synucleins; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein