帕金
泛素连接酶
生物
神经退行性变
路易体
泛素
帕金森病
肌萎缩侧索硬化
基因
细胞生物学
遗传学
疾病
医学
病理
作者
Hideki Shimura,Nobutaka Hattori,Shinichiro Kubo,Yoshikuni Mizuno,Shuichi Asakawa,Shinsei Minoshima,Nobuyoshi Shimizu,Kazuhiro Iwaï,Tomoki Chiba,Keiji Tanaka,Toshiaki Suzuki
出处
期刊:Nature Genetics
[Springer Nature]
日期:2000-07-01
卷期号:25 (3): 302-305
被引量:1874
摘要
Autosomal recessive juvenile parkinsonism (AR-JP), one of the most common familial forms of Parkinson disease, is characterized by selective dopaminergic neural cell death and the absence of the Lewy body, a cytoplasmic inclusion body consisting of aggregates of abnormally accumulated proteins. We previously cloned PARK2, mutations of which cause AR-JP (ref. 2), but the function of the gene product, parkin, remains unknown. We report here that parkin is involved in protein degradation as a ubiquitin-protein ligase collaborating with the ubiquitin-conjugating enzyme UbcH7, and that mutant parkins from AR-JP patients show loss of the ubiquitin-protein ligase activity. Our findings indicate that accumulation of proteins that have yet to be identified causes a selective neural cell death without formation of Lewy bodies. Our findings should enhance the exploration of the molecular mechanisms of neurodegeneration in Parkinson disease as well as in other neurodegenerative diseases that are characterized by involvement of abnormal protein ubiquitination, including Alzheimer disease, other tauopathies, CAG triplet repeat disorders and amyotrophic lateral sclerosis.
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