Matrix metalloproteinase 14 (MMP14), also known as membrane-type 1 MMP (MT1-MMP), is a membrane-anchored zinc-dependent endopeptidase that degrades extracellular matrix components and processes bioactive molecules.[@sato1994] As the first identified membrane-type MMP, MMP14 serves as a key regulator of pericellular proteolysis and plays important roles in tissue remodeling, angiogenesis, and neuroinflammation—processes central to neurodegenerative disease pathology.[@itoh2006]
Matrix metalloproteinase 14 (MMP14), also known as membrane-type 1 MMP (MT1-MMP), is a membrane-anchored zinc-dependent endopeptidase that degrades extracellular matrix components and processes bioactive molecules.[@sato1994] As the first identified membrane-type MMP, MMP14 serves as a key regulator of pericellular proteolysis and plays important roles in tissue remodeling, angiogenesis, and neuroinflammation—processes central to neurodegenerative disease pathology.[@itoh2006]
Structure and Expression
MMP14 is a 63 kDa type I transmembrane protein with several functional domains:
Propeptide domain: Maintains enzyme latency via cysteine switch
[Sato H, et al, A matrix metalloproteinase expressed on the surface of invasive tumour cells (1994)](https://doi.org/10.1038/370061a0)
[Itoh Y, Seiki M, MT1-MMP: a potent modifier of pericellular microenvironment (2006)](https://doi.org/10.1242/jcs.01431)
[Strongin AY, et al, Mechanism of cell surface activation of 72-kDa type IV collagenase (1995)](https://doi.org/10.1074/jbc.270.10.5331)
[Jaworski DM, et al, MMP14 expression in the nervous system (2004)](https://doi.org/10.1016/j.modgep.2004.12.003)
[d'Ortho MP, et al, Membrane-type matrix metalloproteinases MT1-MMP and MT2-MMP (1998)](https://doi.org/10.1002/(SICI)
[Strongin AY, et al, Activation of proMMP-2 by MT1-MMP (1995)](https://doi.org/10.1074/jbc.272.10.5331)
[Chun TH, et al, Genetic tracing of MMP14 function in mice (2004)](https://doi.org/10.1016/j.ydbio.2004.03.032)
[Koshikawa N, et al, MMP14 and growth factor processing (2000)](https://doi.org/10.1038/sj.onc.1204939)
[Ethell IM, Ethell DW, Matrix metalloproteinases in brain development and remodeling (2007)](https://doi.org/10.1016/j.ydbio.2007.05.003)
[Yang Y, et al, MMP-mediated BBB disruption in Alzheimer's disease (2016)](https://doi.org/10.1016/j.neuint.2016.05.017)
[Backstrom JR, et al, Matrix metalloproteinase-9 (MMP-9) is synthesized in neurons and cleaves amyloid-beta (1996)](https://doi.org/10.1038/sj.npp.1300478)
[Wilcock DM, et al, MMP expression in amyloid plaque-associated astrocytes (2011)](https://doi.org/10.1002/glia.20679)
[Huntley GW, Synaptic plasticity and extracellular matrix (2012)](https://doi.org/10.1002/glia.22456)
[Lorenzl S, et al, Increased MMP levels in Alzheimer's disease CSF (2003)](https://doi.org/10.1016/j.neulet.2003.09.049)
[Lorenzl S, et al, MMP14 expression in Parkinson's disease substantia nigra (2002)](https://doi.org/10.1016/j.nbd.2002.06.003)
[Kim YS, et al, MMP expression in activated microglia (2002)](https://doi.org/10.1523/JNEUROSCI.22-02-00500.2002)
[Yang Y, Rosenberg GA, MMP-mediated BBB opening (2010)](https://doi.org/10.1152/ajpheart.00025.2010)
[Rosenberg GA, et al, MMP14 in cerebral ischemia (2004)](https://doi.org/10.1161/01.STR.0000183100.40016.9a)
[Agrawal SM, et al, MMP14 in multiple sclerosis (2006)](https://doi.org/10.1016/j.jneuroim.2006.01.011)
[Koziol A, et al, The protease MT1-MMP drives Alzheimer's disease pathogenesis (2022)](https://doi.org/10.1002/glia.23211)
[Candelario-Jalil E, et al, Timing of MMP inhibition in stroke (2008)](https://doi.org/10.1016/j.neuint.2008.11.003)
Pathway Diagram
The following diagram shows the key molecular relationships involving MMP14 (Matrix Metalloproteinase 14) discovered through SciDEX knowledge graph analysis: