Department of Neurology, Technische Universität Dresden, Fetscherstraße 74, 01307, Dresden, Germany.
Department of Neurology, Städtisches Klinikum Dresden, 01129, Dresden, Germany.
J Neural Transm (Vienna). 2018 Apr;125(4):591-613. doi: 10.1007/s00702-018-1851-y. Epub 2018 Feb 8.
The hallmark of age-related neurodegenerative diseases is the appearance of cellular protein deposits and spreading of this pathology throughout the central nervous system. Growing evidence has shown the involvement and critical role of proteins with prion-like properties in the formation of these characteristic cellular aggregates. Prion-like domains of such proteins with their proposed function in the organization of membraneless organelles are prone for misfolding and promoting further aggregation. Spreading of these toxic aggregates between cells and across tissues can explain the progression of clinical phenotypes and pathology in a stereotypical manner, characteristic for almost every neurodegenerative disease. Here, we want to review the current evidence for the role of prion-like mechanisms in classical neurodegenerative diseases and ALS in particular. We will also discuss an intriguingly central role of the protein TDP-43 in the majority of cases of this devastating disease.
与年龄相关的神经退行性疾病的标志是细胞蛋白沉积物的出现以及这种病理学在中枢神经系统中的传播。越来越多的证据表明，具有朊病毒样特性的蛋白质在这些特征性细胞聚集物的形成中具有牵连和关键作用。这些蛋白质的朊病毒样结构域及其在无膜细胞器组织中的拟议功能易于错误折叠并促进进一步聚集。这些有毒聚集物在细胞之间和组织之间的传播可以以一种典型的方式解释临床表型和病理学的进展，这种方式几乎适用于每一种神经退行性疾病。在这里，我们想回顾一下朊病毒样机制在经典神经退行性疾病，特别是 ALS 中的作用的现有证据。我们还将讨论 TDP-43 蛋白在这种毁灭性疾病的大多数情况下的核心作用。
