Urate mitigates oxidative stress and motor neuron toxicity of astrocytes derived from ALS-linked SOD1G93A mutant mice
Urate mitigates oxidative stress and motor neuron toxicity of astrocytes derived from ALS-linked SOD1G93A mutant mice
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DOI：
10.1016/j.mcn.2018.06.002
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发表时间：
2018-10-01
影响因子：
3.5
通讯作者：
Schwarzschild, Michael A.
中科院分区：
文献类型：
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作者：
Bakshi, Rachit;Xu, Yuehang;Schwarzschild, Michael A.
抗氧化酶超氧化物歧化酶-1（SOD 1）的显性突变导致肌萎缩侧索硬化症（ALS），这是一种以运动神经元丧失为特征的成人发病性神经退行性疾病。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中心机制。来源于突变型SOD 1（G93 A）小鼠模型或患者的星形胶质细胞通过非细胞自主过程在ALS的脊髓运动神经元变性中发挥重要作用。在这里，我们描述了尿酸盐的神经保护作用和机制。尿酸），一种主要的内源性抗氧化剂和有利的ALS进展速率的生物标志物。我们的研究结果表明，尿酸盐对运动神经元损伤引起的突变型星形胶质细胞从SOD 1（G93 A）小鼠或过氧化氢诱导的氧化应激的显着保护作用。总的来说，这些结果暗示了在ALS的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推动治疗运动神经元疾病的新靶点。
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.