Matrix metalloproteinases in the brain and blood-brain barrier: Versatile breakers and makers

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459 Scopus citations

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.

Original languageEnglish
Pages (from-to)1481-1507
Number of pages27
JournalJournal of Cerebral Blood Flow and Metabolism
Volume36
Issue number9
DOIs
StatePublished - Sep 1 2016

Bibliographical note

Publisher Copyright:
© The Author(s) 2016.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Institute of Neurological Disorders and Stroke: NINDS/ NIH R01NS079507 (PI: BB, Co-I: AMSH) and the National Institute on Aging: NIA/NIH R01AG039621 (PI: AMSH, Co-I: BB) of the National Institutes of Health.

FundersFunder number
National Institutes of Health (NIH)
National Institute on AgingR01AG039621
National Institute on Aging
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke CouncilR01NS079507
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council

    Keywords

    • Alzheimer's
    • Blood-brain barrier
    • Parkinson's disease
    • epilepsy
    • inflammation
    • intracranial aneurysm
    • multiple sclerosis
    • neurodegeneration
    • stroke

    ASJC Scopus subject areas

    • Neurology
    • Clinical Neurology
    • Cardiology and Cardiovascular Medicine

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