| Gene Symbol | MMP14 |
| Common Names | MT1-MMP, Membrane-type 1 MMP |
| Protein | [MMP14 Protein](/proteins/mmp14-protein) |
| Location | 14q11.2 |
| NCBI Gene ID | 4323 |
| UniProt | [P50281](https://www.uniprot.org/uniprot/P50281) |
| Aliases | MT1-MMP, MT-MMP, MMP-X1 |
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.[1] 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.[2]
MMP14 is a 63 kDa type I transmembrane protein with several functional domains:
In the central nervous system, MMP14 is expressed by:
MMP14 serves multiple physiological functions:
Extracellular Matrix Remodeling: Degrades collagen types I, II, and III, as well as other matrix proteins.[5]
Activation of Other MMPs: Cleaves and activates proMMP-2 and proMMP-13, amplifying proteolytic cascades.[6]
Angiogenesis: Required for endothelial cell invasion and new blood vessel formation.[7]
Cell Migration: Enables cells to navigate through dense ECM by localized matrix degradation.
Growth Factor Release: Processes latent growth factors to their active forms.[8]
Synaptic Plasticity: Modulates extracellular matrix around synapses, affecting synaptic strength.[9]
MMP14 plays complex roles in Alzheimer's disease:
Blood-Brain Barrier Dysfunction: MMP14 degrades tight junction proteins, contributing to BBB breakdown in AD.[10]
Amyloid-Beta Processing: Can cleave amyloid-beta peptides and amyloid precursor protein, potentially affecting plaque formation.[11]
Neuroinflammation: Upregulated in reactive astrocytes around amyloid plaques, contributing to inflammatory milieu.[12]
Synaptic Function: Perisynaptic ECM degradation by MMP14 may affect synaptic integrity and plasticity.[13]
Elevated MMP14 levels have been reported in AD brains and CSF, correlating with disease severity.[14]
In Parkinson's disease, MMP14 involvement includes:
Dopaminergic Neuron Vulnerability: MMP14 upregulation in the substantia nigra may contribute to neuronal death through ECM disruption.[15]
Neuroinflammation: Activated microglia express MMP14, potentially amplifying inflammatory responses.[16]
Blood-Brain Barrier: MMP14-mediated BBB dysfunction may allow peripheral inflammatory factors into the brain.[17]
MMP14 is significantly upregulated following cerebral ischemia:
In multiple sclerosis, MMP14 contributes to:
Several approaches target MMP14 activity:
Broad-Spectrum MMP Inhibitors: Batimastat, marimastat (limited CNS penetration, off-target effects)
Selective MMP14 Inhibitors:
Natural Inhibitors: Tissue inhibitors of metalloproteinases (TIMPs) naturally regulate MMP14
| Variant | Effect | Disease Association |
|---|---|---|
| Polymorphisms | Altered expression | Cancer progression |
| rs2239008 | Promoter variant | Cardiovascular disease |
| Expression changes | Upregulation | Neurodegenerative disease |
MMP14 interacts with multiple pathways relevant to neurodegeneration:
Sato H, et al. A matrix metalloproteinase expressed on the surface of invasive tumour cells. Nature. 1994. ↩︎
Itoh Y, Seiki M. MT1-MMP: a potent modifier of pericellular microenvironment. Journal of Cell Science. 2006. ↩︎
Strongin AY, et al. Mechanism of cell surface activation of 72-kDa type IV collagenase. Journal of Biological Chemistry. 1995. ↩︎
Jaworski DM, et al. MMP14 expression in the nervous system. Mechanisms of Development. 2004. ↩︎
d'Ortho MP, et al. [Membrane-type matrix metalloproteinases MT1-MMP and MT2-MMP](https://doi.org/10.1002/(SICI). Cancer Research. 1998. ↩︎
Strongin AY, et al. Activation of proMMP-2 by MT1-MMP. Journal of Biological Chemistry. 1995. ↩︎
Chun TH, et al. Genetic tracing of MMP14 function in mice. Developmental Biology. 2004. ↩︎
Koshikawa N, et al. MMP14 and growth factor processing. Oncogene. 2000. ↩︎
Ethell IM, Ethell DW. Matrix metalloproteinases in brain development and remodeling. Developmental Biology. 2007. ↩︎
Yang Y, et al. MMP-mediated BBB disruption in Alzheimer's disease. Neurochemistry International. 2016. ↩︎
Backstrom JR, et al. Matrix metalloproteinase-9 (MMP-9) is synthesized in neurons and cleaves amyloid-beta. Neuropsychopharmacology. 1996. ↩︎
Wilcock DM, et al. MMP expression in amyloid plaque-associated astrocytes. GLIA. 2011. ↩︎
Huntley GW. Synaptic plasticity and extracellular matrix. GLIA. 2012. ↩︎
Lorenzl S, et al. Increased MMP levels in Alzheimer's disease CSF. Neuroscience Letters. 2003. ↩︎
Lorenzl S, et al. MMP14 expression in Parkinson's disease substantia nigra. Neurobiology of Disease. 2002. ↩︎
Kim YS, et al. MMP expression in activated microglia. Journal of Neuroscience. 2002. ↩︎
Yang Y, Rosenberg GA. MMP-mediated BBB opening. American Journal of Physiology-Heart and Circulatory Physiology. 2010. ↩︎
Rosenberg GA, et al. MMP14 in cerebral ischemia. Stroke. 2004. ↩︎
Agrawal SM, et al. MMP14 in multiple sclerosis. Journal of Neuroimmunology. 2006. ↩︎
Koziol A, et al. The protease MT1-MMP drives Alzheimer's disease pathogenesis. GLIA. 2022. ↩︎
Candelario-Jalil E, et al. Timing of MMP inhibition in stroke. Neurochemistry International. 2008. ↩︎