肌萎缩侧索硬化症疾病进展与线粒体功能紊乱

Amyotrophic Lateral Sclerosis Disease Progression and Mitochondrial Dysfunction

肌萎缩侧索硬化症(ALS)是一种典型的神经退行性疾病,其特征是大脑和脊髓中的运动神经元进行性病变。虽然DNA测序技术筛查出众多的ALS致病基因,拓宽了人们对ALS疾病发生的认识,但是这些功能各异的基因导致ALS疾病进程的分子机制仍是有待阐明的。随着基础研究的不断进展,人们发现线粒体的损伤,线粒体的动力学异常以及线粒体自噬等与神经退行性疾病如ALS的发病具有重要联系。在本篇综述中,我们主要讨论了ALS致病基因导致线粒体功能障碍的可能机制,旨在强调线粒体功能障碍在ALS疾病发展中的重要作用。

Amyotrophic lateral sclerosis(ALS)is one of typical neurodegenerative diseases characterized by progres⁃sive degeneration of motor neurons in the brain and/or spinal cord.A large number of ALS pathogenic genes have been screened out by DNA sequencing and broadened our scope with the occurrence of ALS.However,the downstream signal⁃ing pathways of these genes leading to the progression of ALS disease remains unclear.With the continuous progress of ba⁃sic research,it has been found that mitochondrial damage,abnormal mitochondrial dynamics,and mitophagy play impor⁃tant roles in the pathogenesis of neurodegenerative diseases such as ALS.In this review,we mainly discussed the possible mechanism of mitochondrial dysfunction caused by pathogenic genes of ALS,in order to emphasize the importance of mito⁃chondrial dysfunction in the development of ALS.