Kim Changyoun, Lv Guohua, Lee Jun Sung, Jung Byung Chul, Masuda-Suzukake Masami, Hong Chul-Suk, Valera Elvira, Lee He-Jin, Paik Seung R, Hasegawa Masato, Masliah Eliezer, Eliezer David, Lee Seung-Jae
Department of Biomedical Sciences, Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Departments of Neurosciences and Pathology, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
Sci Rep. 2016 Aug 4;6:30891. doi: 10.1038/srep30891.
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.
单一的淀粉样蛋白与多种神经疾病有关，并且能够产生许多具有不同结构的聚集“毒株”。在淀粉样蛋白中，α-突触核蛋白在一组疾病中产生多种蛋白质病模式，如帕金森病（PD）、路易体痴呆（DLB）和多系统萎缩（MSA）。然而，特定构象与不同病理之间的联系，即毒株假说的关键概念，仍然难以捉摸。在这里，我们表明，在细菌内毒素脂多糖（LPS）存在的情况下，α-突触核蛋白产生了一种可自我更新、结构独特的纤维毒株，该毒株在小鼠中持续诱导特定模式的突触核蛋白病。这些结果表明，尽管一级结构相同，但具有可自我更新结构的淀粉样纤维会导致不同类型的蛋白质病，并且接触外源病原体可能导致突触核蛋白病的多样性。
