Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA; Neurobiology of Disease Graduate Program, Mayo Clinic Graduate School of Biomedical Sciences, Jacksonville, FL, USA.
Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA; Neurobiology of Disease Graduate Program, Mayo Clinic Graduate School of Biomedical Sciences, Jacksonville, FL, USA.
Neuron. 2019 Mar 20;101(6):1057-1069. doi: 10.1016/j.neuron.2019.02.032.
Amyotrophic lateral sclerosis (ALS) is an aggressive neurodegenerative disorder that orchestrates an attack on the motor nervous system that is unrelenting. Recent discoveries into the pathogenic consequences of repeat expansions in C9ORF72, which are the most common genetic cause of ALS, combined with the identification of new genetic mutations are providing novel insight into the underlying mechanism(s) that cause ALS. In particular, the myriad of functions linked to ALS-associated genes have collectively implicated four main pathways in disease pathogenesis, including RNA metabolism and translational biology; protein quality control; cytoskeletal integrity and trafficking; and mitochondrial function and transport. Through the identification of common disease mechanisms on which multiple ALS genes converge, key targets for potential therapeutic intervention are highlighted.
肌萎缩侧索硬化症（ALS）是一种侵袭性神经退行性疾病，无情地攻击运动神经系统。最近发现 C9ORF72 重复扩展的致病后果，这是 ALS 的最常见遗传原因，结合新的基因突变的鉴定，为 ALS 致病的潜在机制提供了新的见解。特别是，与 ALS 相关基因相关的众多功能共同暗示了疾病发病机制中的四个主要途径，包括 RNA 代谢和翻译生物学；蛋白质质量控制；细胞骨架完整性和运输；以及线粒体功能和运输。通过鉴定多个 ALS 基因汇聚的常见疾病机制，突出了潜在治疗干预的关键靶点。
