The gelatinases, MMP-2 and MMP-9, as fine tuners of neuroinflammatory processes

Matrix Biol. 2019 Jan:75-76:102-113. doi: 10.1016/j.matbio.2017.11.007. Epub 2017 Nov 21.

Abstract

This review focuses on the complementary roles of MMP-2 and MMP-9 in leukocyte migration into the brain in neuroinflammation, studied mainly in a murine model of experimental autoimmune encephalomyelitis (EAE) that has similarity to the human disease multiple sclerosis. We discuss the cellular sources of MMP-2/MMP-9 in EAE, their sites of activity, and how cleavage of the to-date identified MMP-2/MMP-9 substrates at the blood-brain barrier facilitate leukocyte filtration of the central nervous system (CNS). Where necessary, comparisons are made to inflammatory processes in the periphery and to other MMPs relevant to neuroinflammation. While the general principles concerning MMP-2 and MMP-9 function discussed here are relevant to all inflammatory situations, the details regarding substrates and molecular mechanisms of action are likely to be specific for neuroinflammation.

Keywords: MMP-2 and MMP-9; Neuroinflammation.

Publication types

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

MeSH terms

  • Animals
  • Blood-Brain Barrier / pathology
  • Brain / metabolism
  • Brain / pathology
  • Cell Movement / genetics
  • Central Nervous System / metabolism
  • Central Nervous System / pathology
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / genetics*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Humans
  • Inflammation / genetics*
  • Inflammation / pathology
  • Leukocytes / pathology*
  • Matrix Metalloproteinase 2 / genetics*
  • Matrix Metalloproteinase 9 / genetics*
  • Mice

Substances

  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9