Department of Brain and Neurosciences, Tokyo Metropolitan Institute of Medical Science, Japan.
Department of Brain and Neurosciences, Tokyo Metropolitan Institute of Medical Science, Japan.
Neurochem Int. 2022 Sep;158:105362. doi: 10.1016/j.neuint.2022.105362. Epub 2022 May 31.
Intracellular accumulations and aggregates of abnormal protein, consisting of amyloid-like fibrils, are common neuropathological features of many neurodegenerative diseases. The distributions and spreading of these pathological proteins are closely correlated with clinical symptoms and progression. Recent evidence supports the idea that template-mediated amplification of amyloid-like fibrils and intracellular propagation of fibril seeds are the main mechanisms by which pathological features spread along the neural circuits in the brain. Here, we review recent developments in the structural analysis of amyloid-like fibrils from brains of patients with various types of tauopathy and α-synucleinopathy, focusing on cryo-electron microscopy and mass analysis, and we discuss their relevance to the mechanisms of template-mediated amplification and intracellular propagation.
细胞内异常蛋白质的积累和聚集体，由类淀粉样纤维组成，是许多神经退行性疾病的常见神经病理学特征。这些病理蛋白的分布和扩散与临床症状和进展密切相关。最近的证据支持这样一种观点，即类淀粉样纤维的模板介导扩增和纤维种子的细胞内传播是病理特征沿着大脑神经回路传播的主要机制。在这里，我们回顾了来自各种类型的 tau 病和 α-突触核蛋白病患者大脑中类淀粉样纤维的结构分析的最新进展，重点是低温电子显微镜和质量分析，并讨论了它们与模板介导扩增和细胞内传播机制的相关性。
