Urbanc Brigita
Department of Physics, Drexel University, Philadelphia, Pennsylvania 19104, United States.
J Phys Chem B. 2021 Feb 11;125(5):1307-1316. doi: 10.1021/acs.jpcb.0c07716. Epub 2021 Jan 13.
Amyloid β-protein (Aβ) oligomers are broadly viewed as the proximate mediators of toxicity in Alzheimer's disease (AD). Recent studies, however, provide substantial evidence that Aβ is involved in protection and repair of the central nervous system whereby Aβ oligomer and subsequent fibril formation are integral to its normal antimicrobial and antiviral function. These developments raise a question of what exactly makes Aβ oligomers toxic in the context of AD. This Perspective describes a paradigm shift in the search for toxic Aβ oligomer species that involves oxidative-stress-induced stabilization of Aβ oligomers via cross-linking and reviews most recent research elucidating structural aspects of cross-linked Aβ oligomers and potential inhibition of their toxicity.
淀粉样β蛋白（Aβ）寡聚体被广泛认为是阿尔茨海默病（AD）中毒性的直接介导因子。然而，最近的研究提供了大量证据表明，Aβ参与中枢神经系统的保护和修复，由此Aβ寡聚体及随后的纤维形成对于其正常的抗菌和抗病毒功能不可或缺。这些进展引发了一个问题：在AD的背景下，究竟是什么使得Aβ寡聚体具有毒性。本观点阐述了在寻找有毒Aβ寡聚体种类方面的范式转变，该转变涉及通过交联使Aβ寡聚体发生氧化应激诱导的稳定化，并综述了阐明交联Aβ寡聚体结构方面及其毒性潜在抑制作用的最新研究。
