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Membrane-Type 5 Matrix Metalloproteinase (MT5-MMP): Background and Proposed Roles in Normal Physiology and Disease

Deepak Jadhav1, Anna M Knapinska1, Hongjie Wang1

  • 1Institute for Human Health & Disease Intervention (I-HEALTH) and Department of Chemistry & Biochemistry, Florida Atlantic University, Jupiter, FL 33458, USA.

Biomolecules
|August 28, 2025
PubMed

Insights

Membrane-type 5 matrix metalloproteinase (MT5-MMP) acts as an η-secretase in Alzheimer's disease, cleaving amyloid precursor protein (APP) and increasing synaptotoxic fragments. Further research is needed to define its substrates and develop inhibitors.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Matrix metalloproteinase (MMP) family includes membrane-bound enzymes.
  • Membrane-type 5 matrix metalloproteinase (MT5-MMP) is primarily expressed in the brain and during development.
  • MT5-MMP is implicated in pathologies like Alzheimer's disease and cancer.

Purpose of the Study:

  • To investigate the role of MT5-MMP in Alzheimer's disease pathogenesis.
  • To understand the mechanism by which MT5-MMP contributes to amyloid precursor protein (APP) processing.
  • To identify potential therapeutic targets related to MT5-MMP activity.

Main Methods:

  • Analysis of MT5-MMP expression patterns.
  • Biochemical assays to determine MT5-MMP's enzymatic activity on APP.
  • Identification of intracellular binding partners influencing MT5-MMP activity.

Main Results:

  • MT5-MMP functions as an η-secretase, cleaving APP into synaptotoxic fragments Aη-α and Aη-β.
  • Binding of specific intracellular partners (N4BP2L1, EIG121, BIN1, TMX3) significantly enhances MT5-MMP's η-secretase activity.
  • MT5-MMP may influence APP trafficking and promote proinflammatory responses.

Conclusions:

  • MT5-MMP plays a significant role in the pro-amyloidogenic process in Alzheimer's disease.
  • Understanding MT5-MMP's substrate profile and interactions is crucial.
  • Development of selective MT5-MMP inhibitors is needed for therapeutic considerations.
Keywords:
Alzheimer’s diseaseMT5-MMPcancermembrane-type matrix metalloproteinase

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