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首页> 外文期刊>Expert opinion on therapeutic targets >Glutamate excitotoxicity and therapeutic targets for amyotrophic lateral sclerosis.
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Glutamate excitotoxicity and therapeutic targets for amyotrophic lateral sclerosis.

机译：谷氨酸兴奋性毒性和肌萎缩性侧索硬化症的治疗目标。

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摘要

Two forms of amyotrophic lateral sclerosis (ALS) are known, the familial (FALS), due in part to mutations in superoxide dismutase 1 (SOD1), and the sporadic (SALS), which accounts for > 90% of all cases. The cause of SALS is not known, but excitotoxicity due to overactivation of glutamate receptors may mediate the motor neuron degeneration in the spinal cord, which is the hallmark of this disease. Overactivation of calcium-permeable alpha-amino-3-hydroxy-5-isoxazole propionate receptors lacking the subunit glutamate receptor 2, leading to an increase in calcium cytoplasmic concentration, seems to play an important role in the mechanism of neuronal death. The knowledge of this mechanism, in addition to other factors, provides several possible targets for therapeutic strategies that are reviewed in this article. Some of these strategies have proven to be partially effective in both human mutant superoxide dismutase 1 transgenic rodents (FALS model) and the few existing in vivo models of spinal motor neurodegeneration induced by excitotoxicity (SALS models), although observable benefits are still to be shown in clinical trials.
机译：肌萎缩性侧索硬化症（ALS）有两种形式，一种是家族性（FALS），部分是由于超氧化物歧化酶1（SOD1）的突变，另一种是散发性（SALS），占所有病例的90％以上。 SALS的病因尚不清楚，但是由于谷氨酸受体过度活化引起的兴奋性毒性可能介导脊髓中的运动神经元变性，这是该疾病的标志。缺少亚单位谷氨酸受体2的钙可渗透钙的α-氨基-3-羟基-5-异恶唑丙酸酯受体的过度活化，导致钙细胞质浓度的增加，似乎在神经元死亡的机制中起重要作用。除其他因素外，对该机制的了解还为本文中概述的治疗策略提供了几种可能的靶标。这些策略中的一些已被证明在人类突变型超氧化物歧化酶1转基因啮齿动物（FALS模型）和由兴奋性毒性诱导的脊髓运动神经退行性变的现有体内模型（SALS模型）中均部分有效，尽管仍有可观察到的益处在临床试验中。

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