The conversion of native peptides and proteins into amyloid aggregates is a hallmark of over 50 human disorders, including Alzheimer’s and Parkinson’s diseases. Increasing evidence implicates misfolded protein oligomers produced during the amyloid formation process as the primary cytotoxic agents in many of these devastating conditions. In this review, we analyze the processes by which oligomers are formed, their structures, physicochemical properties, population dynamics, and the mechanisms of their cytotoxicity. We then focus on drug discovery strategies that target the formation of oligomers and their ability to disrupt cell physiology and trigger degenerative processes.

中文翻译：

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错误折叠蛋白质寡聚体：形成机制、细胞毒性作用和针对蛋白质错误折叠疾病的药理学方法


天然肽和蛋白质转化为淀粉样蛋白聚集体是 50 多种人类疾病的标志，包括阿尔茨海默病和帕金森病。越来越多的证据表明，淀粉样蛋白形成过程中产生的错误折叠的蛋白质寡聚体是许多这些破坏性条件下的主要细胞毒剂。在这篇综述中，我们分析了寡聚体的形成过程、其结构、理化性质、群体动态及其细胞毒性机制。然后，我们专注于针对寡聚物的形成及其破坏细胞生理学和触发退行性过程的能力的药物发现策略。