A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds

To address this apparent paradox, we considered the effects on neurons of compounds characterized by alternative redox states of nitrogen monoxide: nitric oxide and nitrosonium ion 8

Stuart A. Lipton; Yun-Beom Choi; Zhuo-Hua Pan; Sizheng Z. Lei; Huei-Sheng Vincent Chen; Nikolaus J. Sucher; Joseph Loscalzo; David J. Singel; Jonathan S. Stamler

2003

Scholarcy highlights

  • CONGENERS of nitrogen monoxide are neuroprotective and neurodestructive1– 7. To address this apparent paradox, we considered the effects on neurons of compounds characterized by alternative redox states of NO: nitric oxide and nitrosonium ion (NO+
  • We report that NO.-mediated neurotoxicity is engendered, at least in part, by reaction with superoxide anion, apparently leading to formation of peroxynitrite, and not by NO. alone
  • The neuroprotective effects of NO result from downregulation of NMDA-receptor activity by reaction with thiol group(s) of the receptor's redox modulatory site1. This reaction is not mediated by NO. itself, but occurs under conditions supporting S-nitrosylation of NMDA receptor thiol
  • The redox versatility of NO allows for its interconversion from neuroprotective to neurotoxic species by a change in the ambient redox milieu
  • The details of this complex redox chemistry of NO may provide a mechanism for harnessing neuroprotective effects and avoiding neurotoxicity in the central nervous system

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