The role of hypernitrosylation in the pathogenesis and pathophysiology of neuroprogressive diseases

Gerwyn Morris, Ken R Walder, André F. Carvalho, Susannah J. Tye, Kurt Lucas, Michael Berk, Michael H J Maes

Research output: Contribution to journalReview ArticleResearchpeer-review

19 Citations (Scopus)

Abstract

There is a wealth of data indicating that de novo protein S-nitrosylation in general and protein transnitrosylation in particular mediates the bulk of nitric oxide signalling. These processes enable redox sensing and facilitate homeostatic regulation of redox dependent protein signalling, function, stability and trafficking. Increased S-nitrosylation in an environment of increasing oxidative and nitrosative stress (O&NS) is initially a protective mechanism aimed at maintaining protein structure and function. When O&NS becomes severe, mechanisms governing denitrosylation and transnitrosylation break down leading to the pathological state referred to as hypernitrosylation (HN). Such a state has been implicated in the pathogenesis and pathophysiology of several neuropsychiatric and neurodegenerative diseases and we investigate its potential role in the development and maintenance of neuroprogressive disorders. In this paper, we propose a model whereby the hypernitrosylation of a range of functional proteins and enzymes lead to changes in activity which conspire to produce at least some of the core abnormalities contributing to the development and maintenance of pathology in these illnesses.

Original languageEnglish
Pages (from-to)453-469
Number of pages17
JournalNeuroscience and Biobehavioral Reviews
Volume84
DOIs
Publication statusPublished - Jan 2018
Externally publishedYes

Keywords

  • Apoptosis
  • MTOR
  • Neurogenesis
  • Neurology
  • Neuroprogression
  • Neurotrophin
  • Nitrosylation
  • NMDA
  • Psychiatry

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