New insights into Parkinson's disease

被引:48
作者
Chung, KKK
Dawson, VL
Dawson, TM
机构
[1] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Dept Neurol, Baltimore, MD 21287 USA
[2] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Dept Neurosci, Baltimore, MD 21287 USA
[3] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Dept Physiol, Baltimore, MD 21287 USA
关键词
parkin; alpha-synuclein; synphilin-1; ubiquitin; proteasome; MPTP;
D O I
10.1007/s00415-003-1304-9
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Parkinson's disease (PD) is the most common neurodegenerative movement disorder. Recent advances in genetics and pathophysiology have led to new insights into the pathogenesis of PD. Ten loci have been linked to hereditary PD. Mutations in alpha-synuclein and ubiquitin carboxy hydrolase L1 (UchL1) cause autosomal dominant PD and mutations in parkin and DJ-1 cause autosomal recessive PD. alpha-Synuclein has emerged as an important protein in the pathogenesis of PD, as it appears to be the major structural component of Lewy bodies and its accumulation/aggregation seems to play a prominent role in sporadic PD. Mutations in parkin are the most common cause of hereditary PD, and mutations in parkin are thought to lead to a loss of parkin's ubiquitin E3 ligase activity. Derangements in parkin function as well as mutations in UCH-L1 fit with the notion that derangements in the ubiquitin proteasomal pathway (UPP) may play important roles in the demise of dopamine neurons in PD. DJ-1 is a protein of unknown function that is linked to autosomal recessive PD. Oxidative stress and impairment in mitochondrial complex I activity are important in sporadic PD, and there is emerging interest in the role of herbicides, fungicides and insecticides that inhibit mitochondrial complex I activity and their role in contributing to the development of PD. These important findings serve as the foundation for discovering new pathways that may lead to the development of new therapies for PD.
引用
收藏
页码:15 / 24
页数:10
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