Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China; Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong University, Shanghai 200240, China.
Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China; State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China.
Structure. 2023 Nov 2;31(11):1335-1347. doi: 10.1016/j.str.2023.08.006. Epub 2023 Aug 31.
Amyloid fibrils are hallmarks of various neurodegenerative diseases. The structural polymorphism of amyloid fibrils holds significant pathological importance in diseases. This review aims to provide an in-depth overview on the complexity of amyloid fibrils' structural polymorphism and its implications in disease pathogenesis. We firstly decipher the molecular rules governing the structural polymorphism of amyloid fibrils. We then discuss pivotal factors that contribute to the assortment of fibril structural polymorphs, including post-translational modifications (PTMs), disease mutations, and interacting molecules, and elucidate the structural basis of how these determinants influence amyloid fibril polymorphism. Furthermore, we underscore the need for a comprehensive understanding of the relationship between diverse fibril polymorphs and pathological activities, as well as their potential roles in therapeutic applications.
淀粉样纤维是各种神经退行性疾病的标志。淀粉样纤维的结构多态性在疾病中具有重要的病理意义。本综述旨在深入了解淀粉样纤维结构多态性的复杂性及其在疾病发病机制中的意义。我们首先揭示了控制淀粉样纤维结构多态性的分子规则。然后，我们讨论了促成纤维结构多态性的关键因素，包括翻译后修饰（PTMs）、疾病突变和相互作用分子，并阐明了这些决定因素如何影响淀粉样纤维多态性的结构基础。此外，我们强调需要全面了解不同纤维多态体与病理活性之间的关系，以及它们在治疗应用中的潜在作用。
