Regulation of inducible nitric oxide synthase gene in glial cells

Antioxid Redox Signal. 2006 May-Jun;8(5-6):929-47. doi: 10.1089/ars.2006.8.929.


Elevated levels of NO produced within the central nervous system (CNS) are associated with the pathogenesis of neuroinflammatory and neurodegenerative human diseases such as multiple sclerosis, HIV dementia, brain ischemia, trauma, Parkinson's disease, and Alzheimer's disease. Resident glial cells in the CNS (astroglia and microglia) express inducible nitric oxide synthase (iNOS) and produce high levels of NO in response to a wide variety of proinflammatory and degenerative stimuli. Although pathways resulting in the expression of iNOS may vary in two different glial cells of different species, the intracellular signaling events required for the expression of iNOS in these cells are slowly becoming clear. Various signaling cascades converge to activate several transcription factors that control the transcription of iNOS in glial cells. The present review summarizes different results and discusses current understandings about signaling mechanisms for the induction of iNOS expression in activated glial cells. A complete understanding of the regulation of iNOS expression in glial cells is expected to identify novel targets for therapeutic intervention in NO-mediated neurological disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bacteria / metabolism
  • Cyclic AMP / metabolism
  • Cytokines / metabolism
  • Gene Expression Regulation, Enzymologic*
  • Humans
  • Mevalonic Acid / metabolism
  • Mitogen-Activated Protein Kinases / metabolism
  • Neuroglia / enzymology*
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoric Monoester Hydrolases / metabolism
  • Protein-Tyrosine Kinases / metabolism
  • Reactive Oxygen Species / metabolism
  • Suppressor of Cytokine Signaling Proteins / metabolism
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Viruses / metabolism


  • Cytokines
  • Reactive Oxygen Species
  • Suppressor of Cytokine Signaling Proteins
  • Transcription Factors
  • Cyclic AMP
  • Nitric Oxide Synthase Type II
  • Phosphatidylinositol 3-Kinases
  • Protein-Tyrosine Kinases
  • Mitogen-Activated Protein Kinases
  • Phosphoric Monoester Hydrolases
  • Mevalonic Acid