Department of Chemistry, Drexel University, Philadelphia, PA 19104, U.S.A.
Biochem Soc Trans. 2024 Aug 28;52(4):1631-1646. doi: 10.1042/BST20230854.
The aggregation of amyloid-beta (Aβ) peptides into cross-β structures forms a variety of distinct fibril conformations, potentially correlating with variations in neurodegenerative disease progression. Recent advances in techniques such as X-ray crystallography, solid-state NMR, and cryo-electron microscopy have enabled the development of high-resolution molecular structures of these polymorphic amyloid fibrils, which are either grown in vitro or isolated from human and transgenic mouse brain tissues. This article reviews our current understanding of the structural polymorphisms in amyloid fibrils formed by Aβ40 and Aβ42, as well as disease-associated mutants of Aβ peptides. The aim is to enhance our understanding of various molecular interactions, including hydrophobic and ionic interactions, within and among cross-β structures.
淀粉样蛋白-β (Aβ) 肽的聚集形成各种不同的交叉-β 结构，可能与神经退行性疾病进展的变化相关。X 射线晶体学、固态 NMR 和低温电子显微镜等技术的最新进展使这些多态性淀粉样纤维的高分辨率分子结构得以发展，这些结构要么在体外生长，要么从人和转基因小鼠脑组织中分离出来。本文综述了我们目前对由 Aβ40 和 Aβ42 形成的淀粉样纤维的结构多态性以及 Aβ肽的疾病相关突变体的理解。目的是增强我们对交叉-β 结构内和之间的各种分子相互作用的理解，包括疏水性和离子相互作用。
