MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom.
Cold Spring Harb Perspect Biol. 2017 Oct 3;9(10):a024141. doi: 10.1101/cshperspect.a024141.
Amyotrophic lateral sclerosis (ALS) is a devastating and rapidly progressive neurodegenerative disease caused by the deterioration of motor neurons. The first symptoms of ALS always begin at a focal but variable site and consistently spread to neighboring regions, suggesting that neurodegeneration in ALS is an orderly and propagating process. Like other neurodegenerative diseases, misfolding of a specific protein is central to ALS. SOD1, the major constituent of the protein deposits in some familial and sporadic forms of ALS, propagates its misfolded conformation like prions, providing a plausible molecular basis for the focality and spreading of muscle weakness in ALS. Because protein misfolding is a common cause of diverse neurodegenerative diseases, strategies aimed at boosting a cell's ability to cope with misfolded proteins could lead to therapeutics to combat these devastating age-related proteinopathies.
肌萎缩侧索硬化症（ALS）是一种由运动神经元退化引起的破坏性和快速进展性神经退行性疾病。ALS 的最初症状总是从一个局部但可变的部位开始，并持续扩散到邻近区域，这表明 ALS 中的神经退行性变是一个有序且扩散的过程。与其他神经退行性疾病一样，特定蛋白质的错误折叠是 ALS 的核心。SOD1 是某些家族性和散发性 ALS 中蛋白沉积物的主要成分，其错误折叠的构象像朊病毒一样传播，为 ALS 中肌肉无力的局灶性和扩散提供了合理的分子基础。由于蛋白质错误折叠是多种神经退行性疾病的共同原因，旨在增强细胞应对错误折叠蛋白质能力的策略可能会导致治疗这些破坏性的与年龄相关的蛋白病的方法。
