肌萎缩侧索硬化症致病基因研究进展

Progress in the Study of ALS Causative Genes

肌萎缩侧索硬化症(amyotrophic lateral sclerosis,ALS)是一种致命性神经退行性疾病,发病率约为0.002%。由于运动神经元发生不可逆的程序性凋亡导致全身肌肉萎缩,患者逐渐失去运动能力,最终因呼吸系统衰竭而窒息。ALS的致病机理尚不明确,目前尚无有效的临床诊断方法。利鲁唑是唯一一个美国食品及药物管理局批准用于治疗ALS的药物,但仅能延长患者几个月的生存期。约有5%的ALS呈家族聚集性,称为家族遗传性ALS(familial ALS,FALS)。目前已发现30多种ALS相关致病基因,一些基因突变的ALS患者可能表现出独特的临床特征,所以致病基因的研究对于ALS的诊断和其作为潜在的药物靶点具有十分重要的意义。该综述对ALS致病基因及其功能进行总结,并对ALS可能存在的致病机理进行了探讨。

Amyotrophic lateral sclerosis（ALS） is a fatal neurodegenerative disease with an incidence of approximately 0.002%. Due to the irreversible and progressive neuronal degeneration of upper motor neurons and lower motor neurons, patients gradually lose their ability to act and eventually die from respiratory failure. The pathogenesis of ALS is not clear, and there are no specific tests to be used as a basis for clinical diagnosis. Riluzole is the only drug approved by the U.S. food and drug administration to treat ALS, however, it can only prolong the patient＇s survival for a few months. Approximately 5% of patients with amyotrophic lateral sclerosis are familial type, known as FALS. And more than 30 causative genes have been identified in FALS at present. Studies have shown that ALS patients with specific genetic mutations may exhibit unique clinical characteristics, so the study of causative genes is of great significance for the diagnosis of ALS and may be potential drug targets for this disease. In this review, we summarized the functions of the causative genes of ALS, and made a bold prediction of the possible pathogenesis of ALS.