Targeting microglia-mediated neurotoxicity: The potential of NOX2 inhibitors

Michael J. Surace, Michelle L. Block

Research output: Contribution to journalReview article

72 Scopus citations

Abstract

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 microgliamediated 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.

Original languageEnglish (US)
Pages (from-to)2409-2427
Number of pages19
JournalCellular and Molecular Life Sciences
Volume69
Issue number14
DOIs
StatePublished - Jul 1 2012

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Keywords

  • Alzheimer's disease
  • Microglia
  • NADPH oxidase
  • NOX2 inhibition
  • Neuroprotection
  • Parkinson's disease
  • ROS
  • Redox

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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