Center for Molecular Medicine, Molecular Cancer Research, University Medical Center Utrecht, Universiteitsweg 100, 3584CG Utrecht, The Netherlands.
Biochem Soc Trans. 2020 Apr 29;48(2):379-397. doi: 10.1042/BST20190054.
It is well established that both an increase in reactive oxygen species (ROS: i.e. O2•-, H2O2 and OH•), as well as protein aggregation, accompany ageing and proteinopathies such as Parkinson's and Alzheimer's disease. However, it is far from clear whether there is a causal relation between the two. This review describes how protein aggregation can be affected both by redox signalling (downstream of H2O2), as well as by ROS-induced damage, and aims to give an overview of the current knowledge of how redox signalling affects protein aggregation and vice versa. Redox signalling has been shown to play roles in almost every step of protein aggregation and amyloid formation, from aggregation initiation to the rapid oligomerization of large amyloids, which tend to be less toxic than oligomeric prefibrillar aggregates. We explore the hypothesis that age-associated elevated ROS production could be part of a redox signalling-dependent-stress response in an attempt to curb protein aggregation and minimize toxicity.
众所周知,活性氧物种(ROS:即 O2•-、H2O2 和 OH•)的增加以及蛋白质聚集伴随着衰老和帕金森病和阿尔茨海默病等蛋白质病的发生。然而,两者之间是否存在因果关系还远不清楚。这篇综述描述了蛋白质聚集如何受到氧化还原信号(H2O2 下游)以及 ROS 诱导的损伤的影响,并旨在概述氧化还原信号如何影响蛋白质聚集以及反之亦然的当前知识。氧化还原信号已被证明在蛋白质聚集和淀粉样蛋白形成的几乎每一个步骤中都发挥作用,从聚集的起始到大淀粉样蛋白的快速寡聚化,后者往往比寡聚前纤维状聚集物毒性更小。我们探讨了这样一种假设,即与年龄相关的 ROS 产生增加可能是氧化还原信号依赖性应激反应的一部分,试图抑制蛋白质聚集并最小化毒性。