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Metalloproteinases and their inhibitors in neurological disease

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Abstract

Matrix metalloproteinases (MMPs) are a group of endopeptidases that degrade the extracellular matrix and are responsible for many physiological and pathological processes. We aim to review the MMP inhibition from a clinical perspective and its possible therapeutic use in the future. MMPs play a role in various neurodegenerative and cerebrovascular diseases such as large artery atherosclerosis and ischemic stroke; for example, MMPs increase blood–brain barrier permeability favoring neuroinflammation. Synthetic MMPs inhibitors have been tested mostly in oncological trials and failed to demonstrate efficacy; some of them were discontinued because of the severe adverse reactions. Tetracyclines, in submicrobial doses, act as an MMP inhibitor, although tetracyclines have not yet been proven effective in several neurological conditions in which they were tested against placebo; it is uncertain whether there may be a use for tetracyclines in cerebrovascular disease, as a neuroprotective agent or in dolichoectasia.

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  1. Department of Neurology, Kliniken Maria Hilf, Moenchengladbach, NRW, Germany

    Edgar R. Lopez-Navarro

  2. Department of Neurology, Columbia University Irving Medical Center, 710 W 168th Street, 6th floor, Suite 639, New York, NY, 10032, USA

    Jose Gutierrez

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JG conceived and designed this review article and revised the manuscript. ELN collected and extracted data and wrote the manuscript. All authors read and approved the manuscript.

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Correspondence to Jose Gutierrez.

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Lopez-Navarro, E.R., Gutierrez, J. Metalloproteinases and their inhibitors in neurological disease. Naunyn-Schmiedeberg's Arch Pharmacol 395, 27–38 (2022). https://doi.org/10.1007/s00210-021-02188-x

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