Dementia Research Project, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo, Japan 156-8506.
Cold Spring Harb Perspect Med. 2018 Mar 1;8(3):a024463. doi: 10.1101/cshperspect.a024463.
The most common neurodegenerative diseases, such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis, are all protein-misfolding diseases and are characterized by the presence of disease-specific protein aggregates in affected neuronal cells. Recent studies have shown that, like tau and α-synuclein, TAR-DNA binding protein of 43 kDa (TDP-43) can form aggregates in vitro in a seed-dependent, self-templating, prion-like manner. Insoluble TDP-43 prepared from the brains of patients has been classified into several strains, which can be transferred from cell to cell in vitro, suggesting the involvement of mechanisms reminiscent of those by which prions spread through the nervous system. The idea that aberrant TDP-43 aggregates propagate in a prion-like manner between cells presents the possibility of novel therapeutic strategies to block spreading of these aggregates throughout the brain.
最常见的神经退行性疾病，如阿尔茨海默病、帕金森病和肌萎缩性侧索硬化症，都是蛋白质错误折叠疾病，其特征是在受影响的神经元细胞中存在特定于疾病的蛋白质聚集物。最近的研究表明，与 tau 和 α-synuclein 一样，43 kDa 的 TAR-DNA 结合蛋白 (TDP-43) 可以在体外以依赖种子、自我模板、类朊病毒的方式形成聚集物。从患者大脑中制备的不溶性 TDP-43 已被分类为几种菌株，这些菌株可以在体外从一个细胞转移到另一个细胞，这表明存在类似于朊病毒通过神经系统传播的机制。异常 TDP-43 聚集物以类朊病毒样方式在细胞间传播的观点提出了一种新的治疗策略的可能性，以阻止这些聚集物在整个大脑中的传播。
