Back
Full-text
Journal article

Microglia antioxidant systems and redox signalling.

  • Vilhardt F Institute of Cellular and Molecular Medicine, Copenhagen University, Copenhagen, Denmark.
  • Haslund-Vinding J Department of Pathology and Immunology, Centre Médical Universitaire, Geneva, Switzerland.
  • Jaquet V UCD School of Biomolecular and Biomedical Science, University College Dublin, Dublin 4, Ireland.
  • McBean G
Show more…
  • 2016-01-13
Published in:
  • British journal of pharmacology. - 2017
Animals
Antioxidants
Humans
Microglia
NADPH Oxidases
Oxidation-Reduction
Signal Transduction
English For many years, microglia, the resident CNS macrophages, have been considered only in the context of pathology, but microglia are also glial cells with important physiological functions. Microglia-derived oxidant production by NADPH oxidase (NOX2) is implicated in many CNS disorders. Oxidants do not stand alone, however, and are not always pernicious. We discuss in general terms, and where available in microglia, GSH synthesis and relation to cystine import and glutamate export, and the thioredoxin system as the most important antioxidative defence mechanism, and further, we discuss in the context of protein thiolation of target redox proteins the necessity for tightly localized, timed and confined oxidant production to work in concert with antioxidant proteins to promote redox signalling. NOX2-mediated redox signalling modulates the acquisition of the classical or alternative microglia activation phenotypes by regulating major transcriptional programs mediated through NF-κB and Nrf2, major regulators of the inflammatory and antioxidant response respectively. As both antioxidants and NOX-derived oxidants are co-secreted, in some instances redox signalling may extend to neighboring cells through modification of surface or cytosolic target proteins. We consider a role for microglia NOX-derived oxidants in paracrine modification of synaptic function through long term depression and in the communication with the adaptive immune system. There is little doubt that a continued foray into the functions of the antioxidant response in microglia will reveal antioxidant proteins as dynamic players in redox signalling, which in concert with NOX-derived oxidants fulfil important roles in the autocrine or paracrine regulation of essential enzymes or transcriptional programs.


LINKED ARTICLES
This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc.
Language
  • English
Open access status
bronze
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/261259
Statistics
Document views: 20 File downloads:
  • fulltext.pdf: 0