# The Potential Use of Matrix Metalloproteinases in Alzheimer’s Disease Therapy

**Authors:** Daria Krawczuk, Barbara Mroczko

PMC · DOI: 10.3390/jcm15041555 · 2026-02-16

## TL;DR

This paper reviews how matrix metalloproteinases (MMPs) could be used in new Alzheimer’s disease therapies, as they have both helpful and harmful effects in the disease.

## Contribution

The paper provides a novel synthesis of how MMPs may be therapeutically modulated in Alzheimer’s disease based on their dual roles.

## Key findings

- MMPs can degrade amyloid but also contribute to blood–brain barrier disruption.
- Their roles are context-dependent, which may explain past therapy failures.
- Selective modulation of MMPs could lead to better Alzheimer’s treatments.

## Abstract

Alzheimer’s disease is the most common cause of dementia and one of the greatest challenges of current medicine. Its pathophysiology is complex, involving β-amyloid deposition, tau hyperphosphorylation, chronic neuroinflammation, and progressive neuronal loss. Despite the introduction of novel therapies, treatment efficacy remains limited, prompting the search for alternative therapeutic targets. One promising area of research focuses on matrix metalloproteinases-proteolytic enzymes involved in tissue remodeling, synaptic plasticity, and inflammatory responses. In the context of AD, MMPs may exert both protective effects, through amyloid degradation, and detrimental effects such as blood–brain barrier disruption and amplification of neuroinflammatory damage. Understanding the dual and context-dependent roles of MMPs may help explain past translational failures and enable the development of more selective, stage-dependent therapeutic strategies. This article is a narrative review summarizing current evidence on the roles of MMPs in AD, with a particular focus on their therapeutic modulation and potential implications for future clinical research. Insights into MMP biology may ultimately guide the design of interventions with improved efficacy and safety for patients with AD.

## Linked entities

- **Proteins:** MAPT (microtubule associated protein tau)
- **Diseases:** Alzheimer’s disease (MONDO:0004975), dementia (MONDO:0001627)

## Full-text entities

- **Genes:** MMP12 (matrix metallopeptidase 12) [NCBI Gene 4321] {aka HME, ME, MME, MMP-12}, App (amyloid beta precursor protein) [NCBI Gene 11820] {aka Abeta, Abpp, Adap, Ag, Cvap, E030013M08Rik}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, A2M (alpha-2-macroglobulin) [NCBI Gene 2] {aka A2MD, CPAMD5, FWP007, S863-7}, Bace1 (beta-site APP cleaving enzyme 1) [NCBI Gene 23821] {aka ASP2, Bace}, APOE (apolipoprotein E) [NCBI Gene 348] {aka AD2, APO-E, ApoE4, LDLCQ5, LPG}, Mmp13 (matrix metallopeptidase 13) [NCBI Gene 17386] {aka Clg, MMP-13, Mmp1}, MMP2 (matrix metallopeptidase 2) [NCBI Gene 4313] {aka CLG4, CLG4A, MMP-2, MMP-II, MONA, TBE-1}, RMDN3 (regulator of microtubule dynamics 3) [NCBI Gene 55177] {aka FAM82A2, FAM82C, RMD-3, RMD3, ptpip51}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, Mmp9 (matrix metallopeptidase 9) [NCBI Gene 17395] {aka B/MMP9, Clg4b, Gel B, MMP-9, pro-MMP-9}, BACE1 (beta-secretase 1) [NCBI Gene 23621] {aka ASP2, BACE, HSPC104}, CLDN5 (claudin 5) [NCBI Gene 7122] {aka AWAL, BEC1, CPETRL1, TMDVCF, TMVCF}, TJP1 (tight junction protein 1) [NCBI Gene 7082] {aka ZO-1}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, TIMP1 (TIMP metallopeptidase inhibitor 1) [NCBI Gene 7076] {aka CLGI, EPA, EPO, HCI, TIMP, TIMP-1}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}, Mmp24 (matrix metallopeptidase 24) [NCBI Gene 17391] {aka MMP-21, MT5-MMP, MT5MMP, MTMMP5}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, TAS2R62P (taste 2 receptor member 62, pseudogene) [NCBI Gene 338399] {aka PS1, T2R62, TAS2R62}, OCLN (occludin) [NCBI Gene 100506658] {aka BLCPMG, PPP1R115, PTORCH1}, MMP14 (matrix metallopeptidase 14) [NCBI Gene 4323] {aka MMP-14, MMP-X1, MT-MMP, MT-MMP 1, MT1-MMP, MT1MMP}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, Mmp3 (matrix metallopeptidase 3) [NCBI Gene 17392] {aka EMS-2, MMP-3, SL-1, SLN-1, SLN1, STR-1}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}
- **Diseases:** amyloidosis (MESH:D000686), neuronal damage (MESH:D009410), gastric adenocarcinoma (MESH:D013274), dementia (MESH:D003704), amyloid (MESH:C000718787), synaptic dysfunction (MESH:C536122), cognitive decline (MESH:D003072), NFTs (MESH:D055956), memory loss (MESH:D008569), neurodegeneration (MESH:D019636), injury to (MESH:D014947), inflammation (MESH:D007249), reactive gliosis (MESH:D005911), amyloid toxicity (MESH:D017772), brain damage (MESH:D001925), MCI (MESH:D060825), AD (MESH:D000544), neurotoxic (MESH:D020258), neurovascular dysfunction (MESH:D013901), vascular dysfunction (MESH:D002561), vascular damage (MESH:D057772), BBB dysfunction (MESH:C536830), toxicity (MESH:D064420), Neuroinflammation (MESH:D000090862)
- **Chemicals:** gadolinium (MESH:D005682), lipopolysaccharides (MESH:D008070), catechin (MESH:D002392), 5xFAD (-), Doxycycline (MESH:D004318), EGCG (MESH:C045651), tetracycline (MESH:D013752), zinc (MESH:D015032), BB-94 (MESH:C080985)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12941445/full.md

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Source: https://tomesphere.com/paper/PMC12941445