Molecular mechanisms of alpha-synuclein neurodegeneration.
Molecular mechanisms of alpha-synuclein neurodegeneration.
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DOI：
10.1016/j.bbadis.2008.09.013
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发表时间：
2009-07
影响因子：
6.2
通讯作者：
Giasson, Benoit I.
中科院分区：
文献类型：
--
作者：
Waxman, Elisa A.;Giasson, Benoit I.
α-突触核蛋白是一种丰富的高电荷蛋白质，通常主要位于突触前末梢的突触小泡周围。尽管这种蛋白质的功能仍不明确，但遗传学研究表明，增加 α-突触核蛋白 (SCNA) 基因拷贝数的点突变或基因改变（重复或三重）可导致帕金森病或相关的路易体痴呆症。 α-突触核蛋白可以异常聚合成具有典型淀粉样蛋白特性的原纤维，这些原纤维是许多类型病理包涵体的主要成分，包括与帕金森病等神经退行性疾病相关的路易体。遗传学研究已经明确证实，α-突触核蛋白基因的改变可导致神经元死亡。尽管有大量证据支持 α-突触核蛋白内含物的毒性，但也有人提出了其他毒性模式，例如寡聚物。在这篇综述中，提出并讨论了 α-突触核蛋白毒性不同机制的一些证据。
α-Synuclein is an abundant highly charged protein that is normally predominantly localized around synaptic vesicles in presynatic terminals. Although the function of this protein is still ill-defined, genetic studies have demonstrated that point mutations or genetic alteration (duplications or triplications) that increase the number of copies of the α-synuclein (SCNA) gene can cause Parkinson’s disease or the related disorder dementia with Lewy bodies. α-Synuclein can aberrantly polymerize into fibrils with typical amyloid properties, and these fibrils are the major component of many types of pathological inclusions, including Lewy bodies, which are associated with neurodegenerative diseases, such as Parkinson’s disease. Genetic studies have clearly established that alteration in the α-synuclein gene can lead to neuronal demise. Although there is substantial evidence supporting the toxic nature of α-synuclein inclusions, other modes of toxicity such as oligomers have been proposed. In this review, some of the evidence for the different mechanisms of α-synuclein toxicity is presented and discussed.
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影响因子：
82.9
作者：
Conway, KA;Harper, JD;Lansbury, PT
通讯作者：
Lansbury, PT
影响因子：
4.7
作者：
Campbell, BCV;McLean, CA;Li, QX
通讯作者：
Li, QX
影响因子：
2.9
作者：
Conway, KA;Harper, JD;Lansbury, PT
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影响因子：
168.9
作者：
Chartier-Harlin, MC;Kachergus, J;Destée, A
通讯作者：
Destée, A
DOI：
10.1073/pnas.97.2.571
发表时间：
2000-01-18
影响因子：
11.1
作者：
Conway, KA;Lee, SJ;Lansbury, PT
通讯作者：
Lansbury, PT