NADPH oxidase inhibition targets deleterious microglial activation. Increasing evidence points to NADPH oxidase (also called phagocytic oxidase (PHOX)) as a critical mechanism of microglia-mediated neuron damage. Traditional anti-inflammatory approaches focus on specific downstream targets, such as prostaglandin E2 (PGE2). However, targeting NADPH oxidase inhibits the global pro-inflammatory response further upstream in the process of neurotoxic microglial activation and is able to inhibit a broad spectrum of cytokines, nitric oxide, and reactive oxygen species to confer neuroprotection. At present, small molecules, peptides, anti-inflammatory cytokines, and an antibiotic have been identified that inhibit microglial NADPH oxidase and are neuroprotective. Further research is warranted to discover the mechanisms through which these seemingly diverse compounds work and to identify more specific inhibitors of this key neurotoxic pathway. This figure is modified from Zhang et al. . IL, interleukin; TNF, tumor necrosis factor.
Block BMC Neuroscience 2008 9(Suppl 2):S8 doi:10.1186/1471-2202-9-S2-S8