Parkin and α-synuclein:: Opponent actions in the pathogenesis of Parkinson's disease

被引:7
作者
Baptista, MJ [1 ]
Cookson, MR [1 ]
Miller, DW [1 ]
机构
[1] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA
关键词
Lewy bodies; mitochondria; parkin; proteasome; synapses; synuclein;
D O I
10.1177/1073858403260392
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Dominant mutations in the gene for alpha-synuclein, a small presynaptic protein, can cause Parkinson's disease. Although there is still substantial debate about the precise mechanisms, alpha-synuclein is toxic to vulnerable neurons, probably as a result of its tendency to aggregate. Opposing this is another gene product that, when mutated, causes a recessive form of parkinsonism, parkin. Parkin has been recently shown to protect cells against alpha-synuclein toxicity. However, the precise details of the mechanism are unclear. This review will discuss the concept that there are multiple neuronal functions that are targeted by mutant alpha-synuclein, and in many cases, there is evidence that parkin can protect cells against damage to the same systems. The authors will also discuss ways in which to test some of these ideas, by using newly identified genes such as DJ-1 that cause similar phenotypes.
引用
收藏
页码:63 / 72
页数:10
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