Targeting microglia-mediated neurotoxicity: the potential of NOX2 inhibitors.
Targeting microglia-mediated neurotoxicity: the potential of NOX2 inhibitors.
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DOI：
10.1007/s00018-012-1015-4
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发表时间：
2012-07
影响因子：
8
通讯作者：
Block, Michelle L.
中科院分区：
文献类型：
--
作者：
Surace, Michael J.;Block, Michelle L.
关键词：
小胶质细胞是中枢神经系统健康的关键哨兵，其功能障碍与神经退行性疾病的进展密切相关。虽然小胶质细胞可以产生许多对邻近神经元有毒的因子，但 NOX2 被认为是小胶质细胞介导的神经毒性的常见且重要的机制。越来越多的证据表明，小胶质细胞中 NOX2 酶复合物的激活具有神经毒性，既会产生损害邻近神经元的细胞外活性氧，也会在小胶质细胞中启动氧化还原信号传导，从而放大促炎症反应。更具体地说，有证据表明 NOX2 氧化还原信号传导增强小胶质细胞对促炎刺激的敏感性，并放大神经毒性细胞因子的产生，从而促进慢性和神经毒性小胶质细胞激活。在这里，我们描述了表明 NOX2 在小胶质细胞介导的神经毒性中作用的证据，重点是阿尔茨海默病和帕金森病，描述了已经测试的可用抑制剂，并详细证明了针对这种酶复合物调节小胶质细胞的神经保护和治疗潜力。
Microglia are key sentinels of central nervous system health and their dysfunction has been widely implicated in the progressive nature of neurodegenerative diseases. While microglia can produce a host of factors that are toxic to neighboring neurons, NOX2 has been implicated as a common and essential mechanism of microglia-mediated neurotoxicity. Accumulating evidence indicates that activation of the NOX2 enzyme complex in microglia is neurotoxic both through the production of extracellular reactive oxygen species that damage neighboring neurons as well as the initiation of redox signaling in microglia that amplifies the pro-inflammatory response. More specifically, evidence supports that NOX2 redox signaling enhances microglial sensitivity to pro-inflammatory stimuli and amplifies the production of neurotoxic cytokines, to promote chronic and neurotoxic microglial activation. Here, we describe the evidence denoting the role of NOX2 in microglia-mediated neurotoxicity with an emphasis on Alzheimer’s and Parkinson’s Disease, describe available inhibitors that have been tested, and detail evidence of the neuroprotective and therapeutic potential of targeting this enzyme complex to regulate microglia.
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影响因子：
8
作者：
Bloom, D;Dhakshinamoorthy, S;Jaiswal, AK
通讯作者：
Jaiswal, AK
影响因子：
5.3
作者：
Atkins, CM;Sweatt, JD
通讯作者：
Sweatt, JD
影响因子：
6.1
作者：
Chechneva, Olga V.;Mayrhofer, Florian;Daugherty, Daniel J.;Pleasure, David E.;Hong, Jau-Shyong;Deng, Wenbin
通讯作者：
Deng, Wenbin
影响因子：
56.9
作者：
ABATE, C;PATEL, L;CURRAN, T
通讯作者：
CURRAN, T
影响因子：
5.3
作者：
Abramov, AY;Jacobson, J;Duchen, MR
通讯作者：
Duchen, MR