Cited by 219Genetics and Neurodevelopmental DisordersProtease and Inhibitor MechanismsNeurogenesis and neuroplasticity mechanisms

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A delicate balance: role of MMP-9 in brain development and pathophysiology of neurodevelopmental disorders.

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Reinhard, Sarah M., Razak, Khaleel, Ethell, Iryna M.·2015·Frontiers in Cellular Neuroscience

DOI 10.3389/fncel.2015.00280PMC PMC4518323

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Abstract

The extracellular matrix (ECM) is a critical regulator of neural network development and plasticity. As neuronal circuits develop, the ECM stabilizes synaptic contacts, while its cleavage has both permissive and active roles in the regulation of plasticity. Matrix metalloproteinase 9 (MMP-9) is a member of a large family of zinc-dependent endopeptidases that can cleave ECM and several cell surface receptors allowing for synaptic and circuit level reorganization. It is becoming increasingly clear that the regulated activity of MMP-9 is critical for central nervous system (CNS) development. In particular, MMP-9 has a role in the development of sensory circuits during early postnatal periods, called 'critical periods.' MMP-9 can regulate sensory-mediated, local circuit reorganization through its ability to control synaptogenesis, axonal pathfinding and myelination. Although activity-dependent activation of MMP-9 at specific synapses plays an important role in multiple plasticity mechanisms throughout the CNS, misregulated activation of the enzyme is implicated in a number of neurodegenerative disorders, including traumatic brain injury, multiple sclerosis, and Alzheimer's disease. Growing evidence also suggests a role for MMP-9 in the pathophysiology of neurodevelopmental disorders including Fragile X Syndrome. This review outlines the various actions of MMP-9 during postnatal brain development, critical for future studies exploring novel therapeutic strategies for neurodevelopmental disorders.

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“Though other MMPs are increased as well, including MMP-2, MMP-3 and TIMP-2 in adults, MMP-9 has the most prominent and consistent increase in protein levels across ages (Konopka et al., 2013).”
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Uhm, 1998, Oligodendrocytes utilize a matrix metalloproteinase, MMP-9, to extend processes along an astrocyte extracellular matrix., Glia, 22, 53, 10.1002/(SICI)1098-1136(199801)22:153::AID-GLIA53.0.CO;2-9 · DOI

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Authors: Reinhard, S. M., Razak, K., & Ethell, I. M.
Affiliations: University of California, Riverside (US)
Corresponding author: Ethell, Iryna M.
ORCID: Razak, Khaleel
Ethell, Iryna M.
Venue: Frontiers in Cellular Neuroscience
Publisher: Frontiers Media SA
Published: 2015-07-29
Volume: 9
Pages: 280-280
ISSN: 1662-5102 (ISSN-L)
DOI: 10.3389/fncel.2015.00280
PMC: PMC4518323
OpenAlex: W1504544942
Cited by: 219
References: 145
Citations by year: 2026: 9 · 2025: 18 · 2024: 16 · 2023: 28 · 2022: 32 · 2021: 34 · 2020: 29 · 2019: 17 · 2018: 14 · 2017: 7 · 2016: 11 · 2015: 4
FWCI: 1.56
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
eScholarship (California Digital Library) (submittedVersion, cc-by)
eScholarship (California Digital Library) (submittedVersion)
Funders: National Science Foundation
FRAXA Research Foundation
National Institute of Mental Health
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords: MMP-9, extracellular matrix, brain development, neurodevelopmental disorders, critical period, synaptogenesis, axon guidance, myelination, synaptic plasticity, fragile X syndrome, traumatic brain injury, multiple sclerosis, Alzheimer's disease

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A delicate balance: role of MMP-9 in brain development and pathophysiology of neurodevelopmental disorders.

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