肌萎缩侧索硬化致病的分子遗传学机制

Molecular Genetic Mechanism of Amyotrophic Lateral Sclerosis

肌萎缩侧索硬化(ALS)是一种与神经退行性密切相关的神经系统变性疾病,临床主要表现为肌肉进行性萎缩,累及呼吸系统可导致呼吸困难,甚至死亡。目前研究的与ALS致病相关的基因突变包括超氧化物歧化酶突变、C9ORF72重复扩增、肉瘤融合蛋白和交互反应DNA结合蛋白-43等,其中研究较为深入的是超氧化物歧化酶突变。近年来也发现了一些新的基因突变与ALS相关。分子遗传学机制将ALS研究由宏观层面过渡到微观层面,有助于进一步揭示ALS的发病机制,也为未来有效治疗ALS提供了作用靶点。

Amyotrophic lateral sclerosis(ALS)is a degenerative disease of the nervous system closely related to neurodegeneration.Its main clinical manifestations are progressive muscle weakness,and the involvement of the respiratory system can lead to dyspnea and even death.Currently,mutations related to ALS pathogenesis include superoxide dismutase mutation,chromosome 9 open reading frame 72(C9ORF72)repeat amplification,sarcoma fusion protein and interactive DNA binding protein-43,among which superoxide dismutase mutation has been studied in depth.In recent years,several new genetic mutations have been found to be associated with ALS.Molecular genetic mechanism has transformed the ALS research from the macroscopic level to the microscopic level,it is helpful to further reveal the pathogenesis of ALS,and also providing a target for the effective treatment of ALS in the future.