Structural and functional characterization of two alpha-synuclein strains
Structural and functional characterization of two alpha-synuclein strains
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DOI：
10.1038/ncomms3575
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发表时间：
2013-10-01
影响因子：
16.6
通讯作者：
Melki, Ronald
中科院分区：
文献类型：
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作者：
Bousset, Luc;Pieri, Laura;Melki, Ronald
α-突触核蛋白聚集与多种疾病有关，包括帕金森氏病、路易体痴呆、纯自主神经衰竭和多系统萎缩。通过感染途径传播的不同菌株的存在，解释了由单一蛋白质组成的蛋白质聚集体与各种临床表型之间的联系。在这里，我们从结构和功能上描述了α-突触核蛋白的两种多态。我们提出的证据表明，这两种形式确实符合被鉴定为两种α-突触核蛋白的分子标准。具体地说，我们发现这两个菌株具有不同的结构、毒性水平以及在体外和体内的播种和繁殖特性。这种菌株的差异可能解释了不同个体/细胞类型和/或联核病类型的疾病进展的差异。
alpha-synuclein aggregation is implicated in a variety of diseases including Parkinson's disease, dementia with Lewy bodies, pure autonomic failure and multiple system atrophy. The association of protein aggregates made of a single protein with a variety of clinical phenotypes has been explained for prion diseases by the existence of different strains that propagate through the infection pathway. Here we structurally and functionally characterize two polymorphs of alpha-synuclein. We present evidence that the two forms indeed fulfil the molecular criteria to be identified as two strains of alpha-synuclein. Specifically, we show that the two strains have different structures, levels of toxicity, and in vitro and in vivo seeding and propagation properties. Such strain differences may account for differences in disease progression in different individuals/cell types and/or types of synucleinopathies.