Inhibition of NADPH oxidase promotes alternative and anti-inflammatory microglial activation during neuroinflammation.
Inhibition of NADPH oxidase promotes alternative and anti-inflammatory microglial activation during neuroinflammation.
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DOI：
10.1111/j.1471-4159.2011.07572.x
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发表时间：
2012-01
影响因子：
4.7
通讯作者：
Bosetti F
中科院分区：
文献类型：
--
作者：
Choi SH;Aid S;Kim HW;Jackson SH;Bosetti F
与巨噬细胞一样，小胶质细胞在功能上被极化成不同的表型激活状态，称为经典和替代。这两种表型的平衡对于确保适当的脑内稳态可能是至关重要的，并且可能在脑病理状态（例如阿尔茨海默病）中改变。我们使用p47 phox和gp 91 phox缺陷小鼠以及apocynin（一种NADPH氧化酶抑制剂）研究了NADPH氧化酶在小胶质细胞活化状态中的作用，apocynin是侧脑室注射LPS或Aβ1-42诱导的神经炎症过程中的一种NADPH氧化酶抑制剂。我们发现NADPH氧化酶在小胶质细胞表型和随后的炎症反应的调节中起着关键作用。我们证明，抑制NADPH氧化酶或其功能性p47 phox亚基的基因缺失将小胶质细胞激活从经典状态切换到炎症挑战的替代状态。此外，我们发现了氧化还原状态向氧化环境的转变，并且小胶质细胞亚群在阿尔茨海默病脑中保留了其有害的表型。小胶质细胞可以改变其活化表型依赖于NADPH氧化酶依赖的氧化还原状态的微环境。NADPH氧化酶的抑制代表了一种有前途的神经保护方法，以减少氧化应激和调节小胶质细胞表型朝向替代状态。
Like macrophages, microglia are functionally polarized into different phenotypic activation states, referred as classical and alternative. The balance of the two phenotypes may be critical to ensure proper brain homeostasis, and may be altered in brain pathological states, such as Alzheimer’s disease. We investigated the role of NADPH oxidase in microglial activation state using p47phox and gp91phox-deficient mice as well as apocynin, a NADPH oxidase inhibitor during neuroinflammation induced by an intracerebroventricular injection of LPS or Aβ1–42. We showed that NADPH oxidase plays a critical role in the modulation of microglial phenotype and subsequent inflammatory response. We demonstrated that inhibition of NADPH oxidase or gene deletion of its functional p47phox subunit switched microglial activation from a classical to an alternative state in response to an inflammatory challenge. Moreover, we showed a shift in redox state towards an oxidized milieu and that subpopulations of microglia retain their detrimental phenotype in Alzheimer’s disease brains. Microglia can change their activation phenotype depending on NADPH oxidase-dependent redox state of microenvironment. Inhibition of NADPH oxidase represents a promising neuroprotective approach to reduce oxidative stress and modulate microglial phenotype towards an alternative state.
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影响因子：
2.4
作者：
Block, Michelle L.
通讯作者：
Block, Michelle L.
DOI：
10.2174/138955708786369582
发表时间：
2008-11
期刊：
Mini reviews in medicinal chemistry
影响因子：
--
作者：
Aliev G;Obrenovich ME;Reddy VP;Shenk JC;Moreira PI;Nunomura A;Zhu X;Smith MA;Perry G
通讯作者：
Perry G
DOI：
10.18632/aging.100021
发表时间：
2009-02-11
期刊：
Aging
影响因子：
--
作者：
Choi SH;Bosetti F
通讯作者：
Bosetti F
影响因子：
6.6
作者：
Bruce-Keller, Annadora J.;Gupta, Sunita;Markesbery, William R.
通讯作者：
Markesbery, William R.
影响因子：
56.9
作者：
Nimmerjahn, A;Kirchhoff, F;Helmchen, F
通讯作者：
Helmchen, F