| Inhibition of NADPH oxidase promotes alternative and anti-inflammatory microglial activation during neuroinflammation. | |
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MedLine Citation:
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PMID: 22050439 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 p47(phox) and gp91(phox) -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 p47(phox) 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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Authors:
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Sang-Ho Choi; Saba Aid; Hyung-Wook Kim; Sharon H Jackson; Francesca Bosetti |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Intramural Date: 2011-11-28 |
Journal Detail:
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Title: Journal of neurochemistry Volume: 120 ISSN: 1471-4159 ISO Abbreviation: J. Neurochem. Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2011-12-20 Completed Date: 2012-02-09 Revised Date: 2012-03-27 |
Medline Journal Info:
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Nlm Unique ID: 2985190R Medline TA: J Neurochem Country: England |
Other Details:
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Languages: eng Pagination: 292-301 Citation Subset: IM |
Copyright Information:
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Published 2011. This article is a US Government work and is in the public domain in the USA. |
Affiliation:
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Molecular Neuroscience Unit, National Institutes of Health, Bethesda, Maryland, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetophenones
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therapeutic use Aged Alzheimer Disease / pathology Animals Antigens, CD11b / genetics, metabolism DNA Helicases / deficiency Encephalitis / chemically induced, drug therapy, metabolism*, pathology* Enzyme Inhibitors / therapeutic use Enzyme-Linked Immunosorbent Assay Female Frontal Lobe / enzymology*, pathology Gene Expression Regulation, Enzymologic / drug effects, physiology* Humans Injections, Intraventricular Lipopolysaccharides / toxicity Male Mice Mice, Inbred C57BL Mice, Knockout Microglia / drug effects, physiology* NADPH Oxidase / metabolism* Postmortem Changes RNA, Messenger / metabolism Receptors, Immunologic / deficiency |
| Chemical | |
Reg. No./Substance:
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0/Acetophenones; 0/Antigens, CD11b; 0/Enzyme Inhibitors; 0/Lipopolysaccharides; 0/Pirb protein, mouse; 0/RNA, Messenger; 0/Receptors, Immunologic; 498-02-2/acetovanillone; EC 1.6.3.1/NADPH Oxidase; EC 3.6.1.-/DNA Helicases; EC 3.6.4.12/RUVBL2 protein, mouse |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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