Academic Neurology Unit and Sheffield Care & Research Centre for Motor Neuron Disorders, Department of Neuroscience, University of Sheffield, Sheffield S10 2RX, UK.
Free Radic Biol Med. 2010 Mar 1;48(5):629-41. doi: 10.1016/j.freeradbiomed.2009.11.018. Epub 2009 Dec 4.
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by death of motor neurons leading to muscle wasting, paralysis, and death, usually within 2-3 years of symptom onset. The causes of ALS are not completely understood, and the neurodegenerative processes involved in disease progression are diverse and complex. There is substantial evidence implicating oxidative stress as a central mechanism by which motor neuron death occurs, including elevated markers of oxidative damage in ALS patient spinal cord and cerebrospinal fluid and mutations in the antioxidant enzyme superoxide dismutase 1 (SOD1) causing approximately 20% of familial ALS cases. However, the precise mechanism(s) by which mutant SOD1 leads to motor neuron degeneration has not been defined with certainty, and the ultimate trigger for increased oxidative stress in non-SOD1 cases remains unclear. Although some antioxidants have shown potential beneficial effects in animal models, human clinical trials of antioxidant therapies have so far been disappointing. Here, the evidence implicating oxidative stress in ALS pathogenesis is reviewed, along with how oxidative damage triggers or exacerbates other neurodegenerative processes, and we review the trials of a variety of antioxidants as potential therapies for ALS.
肌萎缩侧索硬化症（ALS）是一种毁灭性的神经退行性疾病，其特征是运动神经元死亡，导致肌肉消瘦、瘫痪和死亡，通常在症状出现后的 2-3 年内。ALS 的病因尚未完全阐明，疾病进展中涉及的神经退行性过程多种多样且复杂。有大量证据表明氧化应激是运动神经元死亡的一个核心机制，包括 ALS 患者脊髓和脑脊液中氧化损伤标志物的升高，以及抗氧化酶超氧化物歧化酶 1（SOD1）的突变导致约 20%的家族性 ALS 病例。然而，突变 SOD1 导致运动神经元退化的确切机制尚未明确确定，非 SOD1 病例中氧化应激增加的最终触发因素仍不清楚。尽管一些抗氧化剂在动物模型中显示出潜在的有益效果，但迄今为止，抗氧化治疗的人体临床试验令人失望。在这里，我们回顾了氧化应激在 ALS 发病机制中的作用，以及氧化损伤如何引发或加剧其他神经退行性过程，我们还回顾了各种抗氧化剂作为 ALS 潜在治疗方法的试验。
