Taylor J Paul, Brown Robert H, Cleveland Don W
Howard Hughes Medical Institute and the Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
Nature. 2016 Nov 10;539(7628):197-206. doi: 10.1038/nature20413.
Amyotrophic lateral sclerosis (ALS) is a progressive and uniformly fatal neurodegenerative disease. A plethora of genetic factors have been identified that drive the degeneration of motor neurons in ALS, increase susceptibility to the disease or influence the rate of its progression. Emerging themes include dysfunction in RNA metabolism and protein homeostasis, with specific defects in nucleocytoplasmic trafficking, the induction of stress at the endoplasmic reticulum and impaired dynamics of ribonucleoprotein bodies such as RNA granules that assemble through liquid-liquid phase separation. Extraordinary progress in understanding the biology of ALS provides new reasons for optimism that meaningful therapies will be identified.
肌萎缩侧索硬化症（ALS）是一种进行性且无一例外会导致死亡的神经退行性疾病。人们已经确定了大量的遗传因素，这些因素会导致ALS中运动神经元的退化，增加对该疾病的易感性或影响其进展速度。新出现的主题包括RNA代谢和蛋白质稳态功能障碍，具体表现为核质运输缺陷、内质网应激诱导以及通过液-液相分离组装的核糖核蛋白体（如RNA颗粒）动力学受损。在理解ALS生物学方面取得的非凡进展为有望找到有意义的治疗方法提供了新的乐观理由。
