Parkinson's Disease and α-Synuclein Expression

被引：141
作者：
Devine, Michael J. [1 ]
Gwinn, Katrina [2 ]
Singleton, Andrew [3 ]
Hardy, John [1 ]
机构：
[1] UCL Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England
[2] Baylor Coll Med, Houston, TX 77030 USA
[3] NIA, NIH, Bethesda, MD 20892 USA
来源：
MOVEMENT DISORDERS | 2011年 / 26卷 / 12期
基金：
英国医学研究理事会; 英国惠康基金;
关键词：
Parkinsonism; genetics; alpha-synuclein; MULTIPLE SYSTEM ATROPHY; LEWY BODY; IN-VIVO; SNCA DUPLICATION; GENE DUPLICATION; MOUSE MODEL; NEURODEGENERATIVE DISEASE; DOPAMINERGIC-NEURONS; LOCUS TRIPLICATION; MESSENGER-RNA;
D O I：
10.1002/mds.23948
中图分类号：
R74 [神经病学与精神病学];
学科分类号：
摘要：
Genetic studies of Parkinson's disease over the last decade or more have revolutionized our understanding of this condition. alpha-Synuclein was the first gene to be linked to Parkinson's disease, and is arguably the most important: the protein is the principal constituent of Lewy bodies, and variation at its locus is the major genetic risk factor for sporadic disease. Intriguingly, duplications and triplications of the locus, as well as point mutations, cause familial disease. Therefore, subtle alterations of alpha-synuclein expression can manifest with a dramatic phenotype. We outline the clinical impact of alpha-synuclein locus multiplications, and the implications that this has for Parkinson's disease pathogenesis. Finally, we discuss potential strategies for disease-modifying therapies for this currently incurable disorder. (C) 2011 Movement Disorder Society
引用
收藏
页码：2160 / 2168
页数：9
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