Membrane-type 1 metalloproteinase is upregulated in microglia/brain macrophages in neurodegenerative and neuroinflammatory diseases

J Neurosci Res. 2014 Mar;92(3):275-86. doi: 10.1002/jnr.23288. Epub 2013 Dec 9.


We previously reported that glioma cells induce the expression of membrane-type 1 metalloproteinase (MT1-MMP or MMP-14) in tumor-associated microglia/macrophages and promote tumor growth, whereas MMP-14 expression in microglia under physiological conditions is very low. Here, we show that the increase in MMP-14 expression is also found in microglia/macrophages associated with neurodegenerative and neuroinflammatory pathologies in mouse models as well as in human biopsies or post-mortem tissue. We found that microglial/macrophage MMP-14 expression was upregulated in Alzheimer's disease tissue, in active lesions of multiple sclerosis, and in tissue from stage II stroke as well as in the corresponding mouse models for the human diseases. In contrast, we observed no upregulation for MMP-14 in microglia/macrophages in the early phase of stroke or in the corresponding mouse model, in human amyotrophic lateral sclerosis (ALS) tissue or in a mouse model of ALS as well as in human cases of acute brain trauma. These data indicate that MMP-14 expression is not a general marker for activated microglia/macrophages but is upregulated in defined stages of neuroinflammatory and neurodegenerative diseases and that there is generally a good match between mouse models and human brain pathologies.

Keywords: Alzheimer's disease; MMP-14; MT1-MMP; amyotrophic lateral sclerosis; macrophages; metalloproteinase; microglia; multiple sclerosis; neurodegeneration; neuroinflammation; stroke; trauma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / complications
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyotrophic Lateral Sclerosis / complications
  • Amyotrophic Lateral Sclerosis / metabolism
  • Amyotrophic Lateral Sclerosis / pathology
  • Animals
  • Brain / metabolism
  • Brain / pathology*
  • Calcium-Binding Proteins
  • DNA-Binding Proteins / metabolism
  • Disease Models, Animal
  • Encephalitis / etiology
  • Encephalitis / pathology*
  • Glioma / complications
  • Glioma / pathology
  • Humans
  • Macrophages / enzymology*
  • Male
  • Matrix Metalloproteinase 14 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microfilament Proteins
  • Microglia / enzymology*
  • Neurodegenerative Diseases / etiology
  • Neurodegenerative Diseases / pathology*
  • Up-Regulation / physiology*
  • Wounds, Stab / complications
  • Wounds, Stab / pathology


  • AIF1 protein, human
  • Calcium-Binding Proteins
  • DNA-Binding Proteins
  • Microfilament Proteins
  • Matrix Metalloproteinase 14