Department of Neurology, Charles University, Faculty of Medicine and University Hospital Hradec Kralove, 500 05 Hradec Kralove, Czech Republic.
Biomolecules. 2021 Mar 16;11(3):437. doi: 10.3390/biom11030437.
Amyotrophic lateral sclerosis (ALS) affects motor neurons in the cerebral cortex, brainstem and spinal cord and leads to death due to respiratory failure within three to five years. Although the clinical symptoms of this disease were first described in 1869 and it is the most common motor neuron disease and the most common neurodegenerative disease in middle-aged individuals, the exact etiopathogenesis of ALS remains unclear and it remains incurable. However, free oxygen radicals (i.e., molecules containing one or more free electrons) are known to contribute to the pathogenesis of this disease as they very readily bind intracellular structures, leading to functional impairment. Antioxidant enzymes, which are often metalloenzymes, inactivate free oxygen radicals by converting them into a less harmful substance. One of the most important antioxidant enzymes is CuZn superoxide dismutase (SOD1), which is mutated in 20% of cases of the familial form of ALS (fALS) and up to 7% of sporadic ALS (sALS) cases. In addition, the proper functioning of catalase and glutathione peroxidase (GPx) is essential for antioxidant protection. In this review article, we focus on the mechanisms through which these enzymes are involved in the antioxidant response to oxidative stress and thus the pathogenesis of ALS and their potential as therapeutic targets.
肌萎缩侧索硬化症（ALS）影响大脑皮层、脑干和脊髓中的运动神经元，并导致呼吸衰竭在三年内死亡。尽管这种疾病的临床症状于 1869 年首次描述，它是最常见的运动神经元疾病和最常见的中年人群神经退行性疾病，但 ALS 的确切病因发病机制仍不清楚，仍然无法治愈。然而，已知自由氧自由基（即含有一个或多个自由电子的分子）会导致疾病的发病机制，因为它们很容易与细胞内结构结合，导致功能障碍。抗氧化酶，通常是金属酶，通过将其转化为危害较小的物质来使自由氧自由基失活。CuZn 超氧化物歧化酶（SOD1）是最重要的抗氧化酶之一，在 20%的家族性肌萎缩侧索硬化症（fALS）病例和高达 7%的散发性肌萎缩侧索硬化症（sALS）病例中发生突变。此外，过氧化氢酶和谷胱甘肽过氧化物酶（GPx）的正常功能对于抗氧化保护至关重要。在这篇综述文章中，我们重点讨论了这些酶如何参与抗氧化应激的反应，从而参与 ALS 的发病机制，以及它们作为治疗靶点的潜力。
