Siddique T, Deng H X
Department of Neurology, Northwestern University Medical School, Chicago, IL 60611, USA.
Hum Mol Genet. 1996;5 Spec No:1465-70. doi: 10.1093/hmg/5.supplement_1.1465.
Amyotrophic lateral sclerosis (ALS) is a paralytic disorder caused by degeneration of motor neurons in the brain and spinal cord. Identification of mutations in the gene for Cu,Zn superoxide dismutase (SOD1) in a subset of ALS families made it possible to develop a transgenic mouse model of ALS and to investigate its pathogenesis. These investigations suggest that mutant SOD1 acts through a toxic gain of function which may involve generation of free radicals. Conformational change in the mutant SOD1 protein, especially the distortion of the 'rim' of the electrostatic guidance channel may be central to this toxic gain of function and to the pathogenesis of ALS.
肌萎缩侧索硬化症（ALS）是一种由大脑和脊髓中运动神经元退化引起的麻痹性疾病。在一部分ALS家族中，人们发现了铜锌超氧化物歧化酶（SOD1）基因的突变，这使得开发ALS转基因小鼠模型并研究其发病机制成为可能。这些研究表明，突变型SOD1通过功能获得性毒性作用发挥作用，这可能涉及自由基的产生。突变型SOD1蛋白的构象变化，尤其是静电引导通道“边缘”的扭曲，可能是这种功能获得性毒性作用以及ALS发病机制的核心。
