Affiliation:
1. Department of Medical Chemistry, Medical University of Lublin, Lublin, Poland
2. Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Lublin, Poland
3. Department of Pharmacognosy with Medicinal Plants Unit, Medical University of Lublin, Lublin, Poland
Abstract
:
Matrix metalloproteinases (MMPs) play a key role in remodeling of the extracellular
matrix (ECM) and, at the same time, influence cell differentiation, migration, proliferation,
and survival. Their importance in a variety of human diseases including cancer, rheumatoid
arthritis, pulmonary emphysema and fibrotic disorders has been known for many years but
special attention should be paid on the role of MMPs in the central nervous system (CNS)
disorders.
:
Till now, there are not many well documented physiological MMP target proteins in the brain
but only some pathological ones. Numerous neurodegenerative diseases are a consequence of
or result in disturbed remodeling of brain ECM, therefore proper action of MMPs as well as
control of their activity may play crucial roles in the development of these diseases.
:
In the present review, we discuss the role of metalloproteinase inhibitors, from the wellknown
natural endogenous tissue inhibitors of metalloproteinases (TIMPs) to the exogenous
synthetic ones like (4-phenoxyphenylsulfonyl)methylthiirane (SB-3CT), tetracyclines, batimastat
(BB-94) and FN-439. As the MMP-TIMP system has been well described in physiological
development as well as in pathological conditions mainly in neoplastic diseases, the
knowledge about the enzymatic system in mammalian brain tissue still remains poorly understood
in this context. Therefore, we focus on MMPs inhibition in the context of the
physiological function of the adult brain as well as pathological conditions including neurodegenerative
diseases, brain injuries, and others.
Publisher
Bentham Science Publishers Ltd.
Subject
Pharmacology,Molecular Medicine,Drug Discovery,Biochemistry,Organic Chemistry
Cited by
13 articles.
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