The inflammatory NADPH oxidase enzyme modulates motor neuron degeneration in amyotrophic lateral sclerosis mice
The inflammatory NADPH oxidase enzyme modulates motor neuron degeneration in amyotrophic lateral sclerosis mice
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DOI：
10.1073/pnas.0603670103
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发表时间：
2006-08-08
影响因子：
11.1
通讯作者：
Przedborski, Serge
中科院分区：
文献类型：
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作者：
Wu, Du-Chu;Berangere Re, Diane;Przedborski, Serge
AILS 是一种致命性麻痹性疾病，其特征是脊髓运动神经元逐渐丧失。在此，我们发现 NADPH 氧化酶（炎症过程中产生活性氧的主要酶）在 ALS 患者的脊髓以及该疾病的遗传动物模型中的脊髓中被激活。我们证明，ALS 小鼠 NADPH 氧化酶失活可延缓神经退行性变并延长生存期。我们还表明，NADPH 氧化酶衍生的氧化剂产物会损害位于运动神经元上的蛋白质，例如胰岛素样生长因子 1 (IGF1) 受体。我们的体内和体外数据表明，这种氧化修饰阻碍了运动神经元中的 IGF1/Akt 存活途径。这些发现表明，炎症可能加速运动神经元死亡并导致 ALS 中的选择性运动神经元变性，这是一种非细胞自主机制。
AILS is a fatal paralytic disorder characterized by a progressive loss of spinal cord motor neurons. Herein, we show that NADPH oxidase, the main reactive oxygen species-producing enzyme during inflammation, is activated in spinal cords of ALS patients and in spinal cords in a genetic animal model of this disease. We demonstrate that inactivation of NADPH oxidase in ALS mice delays neurodegeneration and extends survival. We also show that NADPH oxidase-derived oxidant products damage proteins such as insulin-like growth factor 1 (IGF1) receptors, which are located on motor neurons. Our in vivo and in vitro data indicate that such an oxidative modification hinders the IGF1/Akt survival pathway in motor neurons. These findings suggest a non-cell-autonomous mechanism through which inflammation could hasten motor neuron death and contribute to the selective motor neuronal degeneration in ALS.