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Matrix metalloproteinases in the brain and blood–brain barrier: Versatile breakers and makers
Abstract
Matrix metalloproteinases are versatile endopeptidases with many different functions in the body in health and disease. In the brain, matrix metalloproteinases are critical for tissue formation, neuronal network remodeling, and blood–brain barrier integrity. Many reviews have been published on matrix metalloproteinases before, most of which focus on the two best studied matrix metalloproteinases, the gelatinases MMP-2 and MMP-9, and their role in one or two diseases. In this review, we provide a broad overview of the role various matrix metalloproteinases play in brain disorders. We summarize and review current knowledge and understanding of matrix metalloproteinases in the brain and at the blood–brain barrier in neuroinflammation, multiple sclerosis, cerebral aneurysms, stroke, epilepsy, Alzheimer’s disease, Parkinson’s disease, and brain cancer. We discuss the detrimental effects matrix metalloproteinases can have in these conditions, contributing to blood–brain barrier leakage, neuroinflammation, neurotoxicity, demyelination, tumor angiogenesis, and cancer metastasis. We also discuss the beneficial role matrix metalloproteinases can play in neuroprotection and anti-inflammation. Finally, we address matrix metalloproteinases as potential therapeutic targets. Together, in this comprehensive review, we summarize current understanding and knowledge of matrix metalloproteinases in the brain and at the blood–brain barrier in brain disorders.
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“Growing evidence has shown that MMPs, especially MMP9, may contribute to cognitive impairment in neurodegenerative diseases through their involvement in blood-brain barrier (BBB) disruption30, a major driving factor for cognitive aging.”
From MT1-MMP inhibition rejuvenates ageing brain and rescues cognitive deficits in obesity (2025) · cites this paper as [30]
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Metadata
- Authors
- Rempe, R. G., Hartz, A. M., & Bauer, B.
- Affiliations
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, USA
- Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2016-07-20
- Volume
- 36
- Issue
- 9
- Pages
- 1481-1507
- ISSN
- 0271-678X
- 1559-7016
- Cited by
- 721
- References
- 24
- Language
- en
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