Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology, Seoul 02792, Korea.
Department of Neurology, Boston University Alzheimer's Disease Center, Boston University School of Medicine, Boston, MA 02118, USA.
Cells. 2020 Dec 15;9(12):2687. doi: 10.3390/cells9122687.
Amyotrophic lateral sclerosis (ALS) is the most frequent motor neuron disease and a neurodegenerative disorder, affecting the upper and/or lower motor neurons. Notably, it invariably leads to death within a few years of onset. Although most ALS cases are sporadic, familial amyotrophic lateral sclerosis (fALS) forms 10% of the cases. In 1993, the first causative gene () of fALS was identified. With rapid advances in genetics, over fifty potentially causative or disease-modifying genes have been found in ALS so far. Accordingly, routine diagnostic tests should encompass the oldest and most frequently mutated ALS genes as well as several new important genetic variants in ALS. Herein, we discuss current literatures on the four newly identified ALS-associated genes (, , , and ) and the previously well-known ALS genes including , , , and . Moreover, we review the pathogenic implications and disease mechanisms of these genes. Elucidation of the cellular and molecular functions of the mutated genes will bring substantial insights for the development of therapeutic approaches to treat ALS.
肌萎缩侧索硬化症（ALS）是最常见的运动神经元疾病和神经退行性疾病，影响上运动神经元和/或下运动神经元。值得注意的是，它通常会在发病后的几年内导致死亡。尽管大多数 ALS 病例是散发性的，但家族性肌萎缩侧索硬化症（fALS）占病例的 10%。1993 年，第一个 fALS 的致病基因（）被鉴定出来。随着遗传学的快速发展，迄今为止，在 ALS 中已经发现了五十多个潜在的致病或疾病修饰基因。因此，常规诊断测试应包括最古老和最常突变的 ALS 基因，以及 ALS 中的几个新的重要遗传变异。在此，我们讨论了最近发现的四个与 ALS 相关的基因（、、、和）的最新文献，以及先前已知的 ALS 基因，包括、、、和。此外，我们回顾了这些基因的致病意义和疾病机制。阐明突变基因的细胞和分子功能将为治疗 ALS 的治疗方法的发展带来实质性的见解。
