Targeting microglia-mediated neurotoxicity

The potential of NOX2 inhibitors

Michael J. Surace, Michelle Block

Research output: Contribution to journalArticle

69 Citations (Scopus)

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 2012
Externally publishedYes

Fingerprint

Microglia
Oxidation-Reduction
Neurons
Enzyme Activation
Poisons
Neurodegenerative Diseases
Parkinson Disease
Reactive Oxygen Species
Alzheimer Disease
Central Nervous System
Cytokines
Health
Enzymes

Keywords

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

ASJC Scopus subject areas

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

Cite this

Targeting microglia-mediated neurotoxicity : The potential of NOX2 inhibitors. / Surace, Michael J.; Block, Michelle.

In: Cellular and Molecular Life Sciences, Vol. 69, No. 14, 07.2012, p. 2409-2427.

Research output: Contribution to journalArticle

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