NADPH oxidase inhibitor DPI is neuroprotective at femtomolar concentrations through inhibition of microglia over-activation

Li Qian, Xi Gao, Zhong Pei, Xuefei Wu, Michelle Block, Belinda Wilson, Jau Shyong Hong, Patrick M. Flood

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

In this paper we report that diphenyliodonium (DPI), a NADPH oxidase inhibitor, shows potent anti-inflammatory and neuroprotective effects at femtomolar concentrations (10-13 to 10-14 M) in primary midbrain cultures. Mechanistic studies revealed that DPI-elicited effects were mediated by the inhibition of LPS-induced microglial ROS production and the subsequent release of pro-inflammatory cytokine TNFa, and the production of nitric oxide. Further studies showed that 10-14 M DPI significantly reduced LPS-induced ERK phosphorylation. Taken together, our results demonstrate that femtomolar concentrations of DPI exert potent anti-inflammatory and neuroprotective effects by inhibiting microglial activation through the inhibition of ERK-regulated PHOX activity.

Original languageEnglish (US)
Pages (from-to)S316-S320
JournalParkinsonism and Related Disorders
Volume13
Issue numberSUPPL. 3
DOIs
StatePublished - Dec 1 2007
Externally publishedYes

Keywords

  • Femtomolar DPI
  • Inflammation
  • LPS
  • Microglia
  • ROS

ASJC Scopus subject areas

  • Neurology
  • Geriatrics and Gerontology
  • Clinical Neurology

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