MMPs in learning and memory and neuropsychiatric disorders
Open accessAbstract
Matrix metalloproteinases (MMPs) are a group of over twenty proteases, operating chiefly extracellularly to cleave components of the extracellular matrix, cell adhesion molecules as well as cytokines and growth factors. By virtue of their expression and activity patterns in animal models and clinical investigations, as well as functional studies with gene knockouts and enzyme inhibitors, MMPs have been demonstrated to play a paramount role in many physiological and pathological processes in the brain. In particular, they have been shown to influence learning and memory processes, as well as major neuropsychiatric disorders such as schizophrenia, various kinds of addiction, epilepsy, fragile X syndrome, and depression. A possible link connecting all those conditions is either physiological or aberrant synaptic plasticity where some MMPs, e.g., MMP-9, have been demonstrated to contribute to the structural and functional reorganization of excitatory synapses that are located on dendritic spines. Another common theme linking the aforementioned pathological conditions is neuroinflammation and MMPs have also been shown to be important mediators of immune responses.
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The ECM can be modified rapidly by the release of proteases, by microglial action and by internalization, all of which can be activated by memory events.
“The ECM can be modified rapidly by the release of proteases [36], by microglial action and by internalization, all of which can be activated by memory events [37–39].”
From The extracellular matrix and perineuronal nets in memory (2022) · cites this paper as [37]
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Autoinducer-2 promotes Pseudomonas aeruginosa PAO1 acute lung infection via the IL-17A pathway
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Belliveau, C., Rahimian, R., Fakhfouri, G., Hosdey, C., Simard, S., Davoli, M. A., Mirault, D., Bruno Giros, A., Turecki, G., & Mechawar, N. (2024) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2024.12.013 · Cited by 11 · see citing works
Type 3 adenylyl cyclase in the MOE is involved in learning and memory in mice
Liu, X., Zhou, Y., Yang, D. J., Li, S., Liu, X., & Wang, Z. (2020) · Behavioural Brain Research · doi:10.1016/j.bbr.2020.112533 · Cited by 11 · see citing works
Orhan, İ. E., Şenol, F. S., Salmas, R. E., Irmak, S., Özgün, Ö., Turgut, G. Ç., Şen, A., Zbancioc, A., Luca, S. V., Skiba, A., et al. (2022) · Chemistry & Biodiversity · doi:10.1002/cbdv.202200315 · Cited by 11 · see citing works
The blood-brain barrier in bipolar disorders: A systematic review
Alonso, C. W., McElhatton, F., O’Mahony, B., Campbell, M., Pollak, T. A., & Stokes, P. R. A. (2024) · Journal of Affective Disorders · doi:10.1016/j.jad.2024.06.032 · Cited by 10 · see citing works
Li, X., Wang, X., Yang, Y., Zhou, J., Wu, X., Zhao, J., Zhang, J., Guo, X., Shao, M., Song, M., et al. (2024) · Schizophrenia · doi:10.1038/s41537-024-00494-w · Cited by 10 · see citing works
Effect of the Matrix Metalloproteinase Inhibitor Doxycycline on Human Trace Fear Memory
Wehrli, J. M., Xia, Y., Offenhammer, B., Kleim, B., Müller, D., & Bach, D. R. (2023) · eNeuro · doi:10.1523/eneuro.0243-22.2023 · Cited by 9 · see citing works
Yang, X., Li, T., Liu, J., Sun, H. B., Cheng, L., Song, X., Han, Z., Luo, H., Han, W., Xie, L., et al. (2023) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14352 · Cited by 10 · see citing works
Attenuating human fear memory retention with minocycline: a randomized placebo-controlled trial
Xia, Y., Wehrli, J. M., Abivardi, A., Hostiuc, M., Kleim, B., & Bach, D. R. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-02732-2 · Cited by 10 · see citing works
Bipolar disorder staging and the impact it has on its management: an update
Dell’Osso, B. M., Cremaschi, L., Macellaro, M., Cafaro, R., & Girone, N. (2024) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2024.2355264 · Cited by 9 · see citing works
Tsilioni, I., Kempuraj, D., & Theoharides, T. C. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26020636 · Cited by 9 · see citing works
Matrix metalloproteinases deregulation in amyotrophic lateral sclerosis
Sánchez-Torres, J. L., Yescas, P., Torres‐Romero, J. C., Espinosa, O. R., López‐Cánovas, L., Tecalco-Cruz, Á. C., Ponce-Regalado, M. D., & Álvarez-Sánchez, M. E. (2020) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2020.117175 · Cited by 9 · see citing works
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Matusiak, M., Oziębło, D., Ołdak, M., Rejmak, E., Kaczmarek, L., Skarzynski, P. H., & Skarżyńśki, H. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-02732-7 · Cited by 9 · see citing works
Self-citationMatrix metalloproteinase activity during methamphetamine cued relapse
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Matrix Metalloproteinase-9 Contributes to Epilepsy Development after Ischemic Stroke in Mice
Pijet, B., Kostrzewska-Księżyk, A., Pijet-Kucicka, M., & Kaczmarek, L. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25020896 · Cited by 8 · see citing works
Self-citationSIRT1, MMP-9 and TIMP-1 levels in children with specific learning disorder
Işık, C. M., Çiçek, A. U., Özbek, D. Ü., & Bakır, S. (2022) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2022.06.015 · Cited by 8 · see citing works
The regulatory function of lncRNA and constructed network in epilepsy
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Cadoret, A., Dion‐Albert, L., Amrani, S., Caron, L., Théberge, M., Turmel, A., Lebel, M., & Ménard, C. (2023) · Behavioural Brain Research · doi:10.1016/j.bbr.2023.114443 · Cited by 8 · see citing works
- Authors
- Beroun, A., Mitra, S., Michaluk, P., Pijet, B., Stefaniuk, M., & Kaczmarek, L.
- Affiliations
- Instytut Biologii Doświadczalnej im. Marcelego Nenckiego (PL)
- Corresponding author
- Kaczmarek, Leszek
- Venue
- Cellular and Molecular Life Sciences
- Published
- 2019-06-06
- Volume
- 76
- Issue
- 16
- Pages
- 3207-3228
- ISSN
- 1420-682X (ISSN-L)
- 1420-9071
- PMC
- PMC6647627
- OpenAlex
- W2954884521
- Cited by
- 207
- References
- 269
- Citations by year
- 2026: 16 · 2025: 24 · 2024: 34 · 2023: 31 · 2022: 40 · 2021: 25 · 2020: 32 · 2019: 4 · 2018: 1
- FWCI
- 2.44
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Cellular and Molecular Life Sciences (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Foundation for Polish Science (BRAINCITY)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- matrix metalloproteinases, MMP-9, learning and memory, neuropsychiatric disorders, schizophrenia, addiction, epilepsy, fragile X syndrome, depression, synaptic plasticity, dendritic spines, neuroinflammation, extracellular matrix, cytokines and growth factors
- MeSH terms
- Animals, Mental Disorders, Brain, Epilepsy, Humans, Learning, Memory, Neuronal Plasticity, Tissue Inhibitor of Metalloproteinases, Matrix Metalloproteinases
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