Morrison B M, Morrison J H, Gordon J W
Neurobiology of Aging Laboratories, Mount Sinai School of Medicine, New York, New York 10029, USA.
J Exp Zool. 1998;282(1-2):32-47.
Amyotrophic lateral sclerosis (ALS) is a devastating neurologic disease characterized by progressive motor dysfunction that leads to paralysis and eventually death. There are numerous hypotheses for the pathogenesis of this disease, but the mechanisms of degeneration were difficult to investigate before the development of animal models. Transgenic mice with alterations in either the superoxide dismutase (SOD-1) or neurofilament genes display motor neuron pathology and deficits in motor function and, therefore, provide animal models for the study of ALS neurodegeneration. Using these animal models, as well as several in vitro models, researchers have made rapid progress during the last several years toward understanding the cause and mechanism of ALS neurodegeneration. These studies have demonstrated that motor neuron degeneration in ALS may be secondary to a number of causes, including neurofilament disruption, mutations in SOD-1, and glutamate excitotoxicity. Although each of these mechanisms can cause motor neuron degeneration by itself, studies of transgenic mice have indicated several points at which these mechanisms may interact, suggesting that they are components of one general mechanism of neurodegeneration.
肌萎缩侧索硬化症（ALS）是一种毁灭性的神经系统疾病，其特征是进行性运动功能障碍，最终导致瘫痪并致人死亡。关于这种疾病的发病机制有众多假说，但在动物模型出现之前，其变性机制很难进行研究。超氧化物歧化酶（SOD - 1）或神经丝基因发生改变的转基因小鼠表现出运动神经元病变以及运动功能缺陷，因此为研究ALS神经变性提供了动物模型。利用这些动物模型以及一些体外模型，研究人员在过去几年里在理解ALS神经变性的原因和机制方面取得了快速进展。这些研究表明，ALS中的运动神经元变性可能继发于多种原因，包括神经丝破坏、SOD - 1突变和谷氨酸兴奋性毒性。虽然这些机制中的每一种都能单独导致运动神经元变性，但对转基因小鼠的研究表明了这些机制可能相互作用的几个点，这表明它们是神经变性一种一般机制的组成部分。
