Although Charcot described amyotrophic lateral sclerosis (ALS) more than 130 years ago, the mechanism underlying the characteristic selective degeneration and death of motor neurons in this common adult motor neuron disease has remained a mystery. There is no effective remedy for this progressive, fatal disorder. Modern genetics has now identified mutations in one gene [Cu/Zn superoxide dismutase (SOD1)] as a primary cause and implicated others [encoding neurofilaments, cytoplasmic dynein and its processivity factor dynactin, and vascular endothelial growth factor (VEGF)] as contributors to, or causes of, motor neuron diseases. These insights have enabled development of model systems to test hypotheses of disease mechanism and potential therapies. Along with errors in the handling of synaptic glutamate and the potential excitotoxic response this provokes, these model systems highlight the involvement of nonneuronal cells in disease progression and provide new therapeutic strategies.

中文翻译：

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揭示涉及ALS运动神经元变性的机制。

尽管Charcot在130多年前就描述了肌萎缩性侧索硬化症（ALS），但在这种常见的成人运动神经元疾病中，运动神经元的特征性选择性变性和死亡的潜在机制仍是一个谜。没有针对这种进行性致命疾病的有效疗法。现代遗传学现已发现一个基因[Cu / Zn超氧化物歧化酶（SOD1）]中的突变是主要原因，并牵涉其他[编码神经丝，细胞质动力蛋白及其合成因子动力蛋白和血管内皮生长因子（VEGF）]的原因或运动神经元疾病的原因。这些见解使能够开发模型系统来测试疾病机理和潜在疗法的假设。