Abstract：
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease mainly characterized by the accumulation of ubiquitinated proteins in the affected motor neurons. At present, the accurate pathogenesis of ALS remains unclear and there are still no effective treatment measures for ALS. The potential pathogenesis of ALS mainly includes the misfolding of some pathogenic proteins, the genetic variation, mitochondrial dysfunction, autophagy disorders, neuroinflammation, the misregulation of RNA, the altered axonal transport, and gut microbial dysbiosis. Exploring the pathogenesis of ALS is a critical step in searching for the effective therapeutic approaches. The current studies suggested that the genetic variation, gut microbial dysbiosis, the activation of glial cells, and the transportation disorder of extracellular vesicles may play some important roles in the pathogenesis of ALS. This review conducts a systematic review of these current potential promising topics closely related to the pathogenesis of ALS; it aims to provide some new evidences and clues for searching the novel treatment measures of ALS.
摘要：
肌萎缩侧索硬化症（ALS）是一种致命的神经退行性疾病，其主要特征是受影响的运动神经元中泛素化蛋白的积累。目前,ALS的确切发病机制尚不清楚,目前尚无有效的治疗措施。ALS的潜在发病机制主要包括一些致病蛋白的错误折叠,遗传变异,线粒体功能障碍，自噬障碍，神经炎症，RNA的错误调控，改变了轴突运输，和肠道微生物菌群失调。探索ALS的发病机制是寻找有效治疗方法的关键步骤。目前的研究表明，遗传变异，肠道微生物菌群失调，神经胶质细胞的激活，细胞外囊泡的运输障碍可能在ALS的发病中起着重要作用。本综述对目前这些与ALS发病机制密切相关的潜在有希望的话题进行了系统的综述，旨在为寻找ALS的新治疗措施提供一些新的证据和线索。
