Department of Clinical Neurological Sciences, Robarts Research Institute, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada.
Curr Opin Neurol. 2017 Dec;30(6):599-607. doi: 10.1097/WCO.0000000000000488.
The current review will examine the contemporary evidence that amyotrophic lateral sclerosis (ALS) is a syndrome in which the unifying feature is a progressive loss of upper and lower motor neuron function.
Although ALS is traditionally viewed as a neurodegenerative disorder affecting the motor neurons, there is considerable phenotypic heterogeneity and widespread involvement of the central nervous system. A broad range of both causative and disease modifying genetic variants are associated with both sporadic and familial forms of ALS. A significant proportion of ALS patients have an associated frontotemporal dysfunction which can be a harbinger of a significantly shorter survival and for which there is increasing evidence of a fundamental disruption of tau metabolism in those affected individuals. Although the traditional neuropathology of the degenerating motor neurons in ALS is that of neuronal cytoplasmic inclusions composed neuronal intermediate filaments, the presence of neuronal cytoplasmic inclusions composed of RNA binding proteins suggests a key role for RNA dysmetabolism in the pathogenesis of ALS.
ALS is a complex multisystem neurodegenerative syndrome with marked heterogeneity at not only the level of clinical expression, but also etiologically.
本次综述将考察目前有关肌萎缩侧索硬化症（ALS）的证据，该证据表明 ALS 是以进行性上运动神经元和下运动神经元功能丧失为特征的综合征。
尽管 ALS 传统上被视为一种影响运动神经元的神经退行性疾病，但它存在相当大的表型异质性和中枢神经系统的广泛受累。广泛的致病和疾病修饰基因变异与散发性和家族性 ALS 均相关。相当一部分 ALS 患者存在相关的额颞叶功能障碍，这预示着患者的生存时间明显缩短，越来越多的证据表明，受影响个体的 Tau 代谢存在根本紊乱。尽管 ALS 中退化的运动神经元的传统神经病理学表现为神经元细胞浆内包含神经元中间丝的包涵体，但由 RNA 结合蛋白组成的神经元细胞浆内包涵体表明，RNA 代谢异常在 ALS 的发病机制中起着关键作用。
ALS 是一种复杂的多系统神经退行性综合征，不仅在临床表型上，而且在病因上都具有明显的异质性。
