Amino acid determinants of alpha-synuclein aggregation: putting together pieces of the puzzle.
Amino acid determinants of alpha-synuclein aggregation: putting together pieces of the puzzle.
复制标题
α-突触核蛋白聚集的氨基酸决定因素：将拼图的各个部分拼凑在一起。
DOI：
10.1016/s0014-5793(02)02883-1
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发表时间：
2002
期刊：
影响因子：
3.5
通讯作者：
Fink,AnthonyL
中科院分区：
文献类型：
--
作者：
Uversky,VladimirN;Fink,AnthonyL
帕金森氏病是第二常见的神经退行性疾病，由黑质多巴胺能神经元的丧失引起。α-突触核蛋白以细胞内蛋白聚集体（路易小体和路易神经突）的形式聚集和纤颤已被认为是该疾病以及其他几种神经退行性疾病的致病因素，包括路易小体痴呆、路易小体变型阿尔茨海默病、多系统萎缩和哈勒vorden - spatz病。因此，α-突触核蛋白的聚集形式在突触核蛋白病的发病机制中起着至关重要的作用。然而，α-突触核蛋白聚集成特定丝状包涵体的分子机制直到最近才为人所知。本文分析了人α-、β-和γ-突触核蛋白、小鼠α-突触核蛋白和家族性帕金森病α-突触核蛋白突变体（A30P和A53T）的聚集和纤颤特性数据，以阐明突触核蛋白聚集的氨基酸决定因素。
Parkinson’s disease is the second most common neurodegenerative disease, and results from loss of dopaminergic neurons in the substantia nigra. The aggregation and fibrillation of α-synuclein in the form of intracellular proteinaceous aggregates (Lewy bodies and Lewy neurites) have been implicated as a causative factor in this disease, as well as in several other neurodegenerative disorders, including dementia with Lewy bodies, Lewy body variant of Alzheimer’s disease, multiple system atrophy and Hallervorden–Spatz disease. Thus, the aggregated forms of α-synuclein play a crucial role in the pathogenesis of the synucleinopathies. However, the molecular mechanisms underlying α-synuclein aggregation into specific filamentous inclusions remained unknown until recently. Data on the aggregation and fibrillation properties of human α-, β- and γ-synucleins, mouse α-synuclein and familial Parkinson’s disease mutants of human α-synuclein (A30P and A53T) are analyzed in order to shed light on the amino acid determinants of synuclein aggregation.