Extracellular matrix degradation by metalloproteinases and central nervous system diseases
Abstract
Matrix metalloproteinases (MMPs) are a gene family of neutral proteases involved in normal and pathological processes in the central nervous system (CNS). Normally released into the extracellular space, MMPs break down the extracellular matrix (ECM) to allow cell growth and to facilitate remodeling. Proteolysis becomes pathological when the normal balance between the proteases and their inhibitors, tissue inhibitors to metalloproteinases (TIMPs), is lost. Cancer cells secrete neutral proteases to facilitate spread through the ECM. MMPs increase capillary permeability, and they have been implicated in demyelination. Neurological diseases, such as brain tumors, multiple sclerosis, Guillain-Barré, ischemia, Alzheimer's disease, and infections, lead to an increase in the matrix-degrading proteases. Two classes of neutral proteases have been extensively studied, namely the MMPs and the plasminogen activators (PAs), which act in concert to attack the ECM. After proteolytic injury occurs, the process of ECM remodeling begins, which can lead to fibrosis of blood vessels and gliosis. TIMPs are increased after the acute injury and may add to the fibrotic buildup of ECM components. Thus, an imbalance in proteolytic activity either during the acute injury or in recovery may aggravate the underlying disease process. Agents that affect the proteolytic process at any of the regulating sites are potentially useful in therapy.
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Glu may cause an increase in MMP expression and activity level.
“Note that Glu may also cause an increase in MMP expression and activity level as reported by a recent study41.”
From Perineuronal nets decrease membrane capacitance of peritumoral fast spiking interneurons in a model of epilepsy (2018) · cites this paper as [41]
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- Authors
- Lukes, A., Mun-Bryce, S., Lukes, M., & Rosenberg, G. A.
- Affiliations
- University of New Mexico (US)
- Corresponding author
- Lukes, Anton
- ORCID
- Rosenberg, Gary A.
- Venue
- Molecular Neurobiology
- Published
- 1999-06
- Volume
- 19
- Issue
- 3
- Pages
- 267-284
- ISSN
- 0893-7648 (ISSN-L)
- 1559-1182
- OpenAlex
- W2004085515
- Cited by
- 230
- References
- 108
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 5 · 2022: 3 · 2021: 6 · 2020: 2 · 2019: 2 · 2018: 5 · 2017: 6 · 2016: 7 · 2015: 6 · 2014: 9 · 2013: 3 · 2012: 10
- FWCI
- 1.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Molecular Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5s06gm008139-21)
- National Institute of General Medical Sciences (GM08139)
- National Institute of Neurological Disorders and Stroke (R01NS021169, NS R01-NS-21169)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Calpain Protease Function and Regulation
- Keywords
- matrix metalloproteinases, extracellular matrix degradation, tissue inhibitors of metalloproteinases, plasminogen activator, central nervous system disorders, demyelination, gliosis, vascular fibrosis, capillary permeability, multiple sclerosis, Alzheimer's disease, brain tumors, Guillain-Barré syndrome, ischemia, neuroinflammation, protease inhibitors
- MeSH terms
- Animals, Blood-Brain Barrier, Central Nervous System Diseases, Extracellular Matrix, Growth Substances, Humans, Metalloendopeptidases, Tissue Inhibitor of Metalloproteinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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