Exposure to bacterial endotoxin generates a distinct strain of α-synuclein fibril.
Exposure to bacterial endotoxin generates a distinct strain of α-synuclein fibril.
复制标题
DOI：
10.1038/srep30891
复制
发表时间：
2016-08-04
影响因子：
4.6
通讯作者：
Lee SJ
中科院分区：
文献类型：
--
作者：
Kim C;Lv G;Lee JS;Jung BC;Masuda-Suzukake M;Hong CS;Valera E;Lee HJ;Paik SR;Hasegawa M;Masliah E;Eliezer D;Lee SJ
一种单一的淀粉样蛋白与多种神经系统疾病有关，并能产生许多具有不同结构的聚集体“菌株”。在淀粉样蛋白中，α-突触核蛋白在一组疾病如帕金森病（PD）、路易体痴呆（DLB）和多系统萎缩（MSA）中产生多种蛋白质病模式。然而，特定的构象和不同的病理之间的联系，应变假说的关键概念，仍然难以捉摸。在这里，我们表明，在细菌内毒素，脂多糖（LPS），α-突触核蛋白的存在下，产生一个自我更新，结构独特的原纤维菌株，一贯诱导小鼠突触核蛋白病的特定模式。这些结果表明，淀粉样蛋白原纤维与自我更新的结构，导致不同类型的蛋白质病，尽管相同的一级结构和暴露于外源性病原体可能有助于突触核蛋白病的多样性。
A single amyloidogenic protein is implicated in multiple neurological diseases and capable of generating a number of aggregate “strains” with distinct structures. Among the amyloidogenic proteins, α-synuclein generates multiple patterns of proteinopathies in a group of diseases, such as Parkinson disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). However, the link between specific conformations and distinct pathologies, the key concept of the strain hypothesis, remains elusive. Here we show that in the presence of bacterial endotoxin, lipopolysaccharide (LPS), α-synuclein generated a self-renewable, structurally distinct fibril strain that consistently induced specific patterns of synucleinopathies in mice. These results suggest that amyloid fibrils with self-renewable structures cause distinct types of proteinopathies despite the identical primary structure and that exposure to exogenous pathogens may contribute to the diversity of synucleinopathies.