Dominant mutations in an antioxidant enzyme superoxide dismutase-1 (SOD1) cause amyotrophic lateral sclerosis (ALS), an adult-onset neurodegenerative disease characterized by loss of motor neurons. Oxidative stress has also been linked to many of the neurodegenerative diseases and is likely a central mechanism of motor neuron death in ALS. Astrocytes derived from mutant SOD1^G93A mouse models or patients play a significant role in the degeneration of spinal motor neurons in ALS through a non-cell-autonomous process. Here we characterize the neuroprotective effects and mechanisms of urate (a.k.a. uric acid), a major endogenous antioxidant and a biomarker of favorable ALS progression rates, in a cellular model of ALS. Our results demonstrate a significant protective effect of urate against motor neuron injury evoked by mutant astrocytes derived from SOD1^G93A mice or hydrogen peroxide induced oxidative stress. Overall, these results implicate astrocyte dependent protective effect of urate in a cellular model of ALS. These findings together with our biomarker data may advance novel targets for treating motor neuron disease.

抗氧化酶超氧化物歧化酶-1（SOD1）中的显着突变会引起肌萎缩性侧索硬化症（ALS），这是一种以运动神经元缺失为特征的成年发作的神经退行性疾病。氧化应激也与许多神经退行性疾病有关，并且可能是ALS中运动神经元死亡的主要机制。源自突变型SOD1 ^G93A的星形胶质细胞小鼠模型或患者通过非细胞自主过程在ALS的脊髓运动神经元变性中起重要作用。在这里，我们在ALS细胞模型中表征了尿酸盐（又称尿酸），主要的内源性抗氧化剂和有利的ALS进展率的生物标志物的神经保护作用和机制。我们的研究结果表明，尿酸盐对由SOD1 ^G93A小鼠衍生的突变星形胶质细胞或过氧化氢诱导的氧化应激引起的运动神经元损伤具有明显的保护作用。总体而言，这些结果暗示在ALS细胞模型中尿酸盐的星形胶质细胞依赖性保护作用。这些发现以及我们的生物标志物数据可能会为治疗运动神经元疾病提供新的靶点。