The role of microglial activation in disease progression

Mult Scler. 2014 Sep;20(10):1288-95. doi: 10.1177/1352458514533230. Epub 2014 May 8.

Abstract

Microglia, a unique type of myeloid cell, play a key role in the inflammation-mediated neurodegeneration occurring during both acute and chronic stages of multiple sclerosis (MS). These highly specialized cells trigger neurotoxic pathways, producing pro-inflammatory cytokines, reactive oxygen and nitrogen species and proteolytic enzymes, causing progressive neurodegeneration. Microglia have also been associated with development of cortical lesions in progressive MS, as well as with alterations of synaptic transmission in experimental autoimmune encephalomyelitis (EAE). However, they also play an important role in the promotion of neuroprotection, downregulation of inflammation, and stimulation of tissue repair. Notably, microglia undergo changes in morphology and function with normal aging, resulting in a decline of their ability to repair central nervous system damage, making axons and neurons more vulnerable with age. Modulation of microglial activation for therapeutic purposes must consider suppressing deleterious effects of these cells, while simultaneously preserving their protective functions.

Keywords: Multiple sclerosis; autoimmunity; axon; microglia; progressive multiple sclerosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Age Factors
  • Animals
  • Cytokines / immunology
  • Cytokines / metabolism
  • Disease Progression
  • Humans
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism
  • Microglia / drug effects
  • Microglia / immunology
  • Microglia / metabolism*
  • Microglia / pathology
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / metabolism*
  • Multiple Sclerosis / pathology
  • Multiple Sclerosis / physiopathology
  • Oxidative Stress
  • Phenotype
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Synaptic Transmission

Substances

  • Cytokines
  • Inflammation Mediators
  • Reactive Oxygen Species