Melki Ronald
J Parkinsons Dis. 2015;5(2):217-27. doi: 10.3233/JPD-150543.
Misfolded protein aggregates are the hallmark of several neurodegenerative diseases in humans. The main protein constituent of these aggregates and the regions within the brain that are affected differ from one neurodegenerative disorder to another. A plethora of reports suggest that distinct diseases have in common the ability of protein aggregates to spread and amplify within the central nervous system. This review summarizes briefly what is known about the nature of the protein aggregates that are infectious and the reason they are toxic to cells. The chameleon property of polypeptides which aggregation into distinct high-molecular weight assemblies is associated to different diseases, in particular, that of alpha-synuclein which aggregation is the hallmark of distinct synucleinopathies, is discussed. Finally, strategies targeting the formation and propagation of structurally distinct alpha-synuclein assemblies associated to different synucleinopathies are presented and their therapeutic and diagnostic potential is discussed.
错误折叠的蛋白质聚集体是人类多种神经退行性疾病的标志。这些聚集体的主要蛋白质成分以及大脑中受影响的区域因神经退行性疾病的不同而有所差异。大量报告表明，不同疾病的蛋白质聚集体在中枢神经系统内具有传播和扩增的共同能力。本综述简要总结了关于具有传染性的蛋白质聚集体的性质以及它们对细胞有毒性的原因的已知信息。讨论了多肽的变色龙特性，即多肽聚集形成不同的高分子量聚集体与不同疾病相关，特别是α-突触核蛋白的特性，其聚集是不同突触核蛋白病的标志。最后，介绍了针对与不同突触核蛋白病相关的结构不同的α-突触核蛋白聚集体的形成和传播的策略，并讨论了它们的治疗和诊断潜力。
