The ubiquitin pathway in Parkinson's disease

被引：1226
作者：
Leroy, E
Boyer, R
Auburger, G
Leube, B
Ulm, G
Mezey, E
Harta, G
Brownstein, MJ
Jonnalagada, S
Chernova, T
Dehejia, A
Lavedan, C
Gasser, T
Steinbach, PJ
Wilkinson, KD
Polymeropoulos, MH
机构：
[1] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA
[2] Univ Hosp Dusseldorf, Dept Neurol, D-40001 Dusseldorf, Germany
[3] Paracelcus Elena Klin, D-34128 Kassel, Germany
[4] NINDS, Basic Neurosci Program, NIH, Bethesda, MD 20892 USA
[5] NIMH, Genet Sect, NIH, Bethesda, MD 20892 USA
[6] Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA
[7] Univ Munich, Klinikum Grosshadern, Neurol Klin, D-8000 Munich, Germany
[8] NIH, Ctr Mol Modeling, CIT, Bethesda, MD 20892 USA
来源：
NATURE | 1998年 / 395卷 / 6701期
关键词：
D O I：
10.1038/26652
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Mutations of the α-synuclein gene1,2 have been identified in some familial forms of Parkinson's disease, and α-synuclein protein has been shown to accumulate in the brains of patients with the disease3. These findings suggest that Parkinson's disease may be caused by the abnormal aggregation of α-synuclein protein. Here we have identified in a German family with Parkinson's disease a missense mutation in the ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) gene. We show that this mutation, Ile93Met, causes a partial loss of the catalytic activity of this thiol protease, which could lead to aberrations in the proteolytic pathway and aggregation of proteins.
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页码：451 / 452
页数：2
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