Authors

Y. S. Kim;T. H. Joh

Comments

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Abbreviated Journal Title

Biomol. Ther.

Keywords

Matrix metalloproteinases; MMP-3; Parkinson's disease; Microglia; Neurodegenerative disorders; FOCAL CEREBRAL-ISCHEMIA; CENTRAL-NERVOUS-SYSTEM; TUMOR-NECROSIS-FACTOR; RABBIT SYNOVIAL FIBROBLASTS; ALPHA-SYNUCLEIN AGGREGATION; MULTIPLE-SCLEROSIS LESIONS; ACTIVATED PROTEIN-KINASE; GELATINASE-B; MMP-9; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; Biochemistry & Molecular Biology; Pharmacology & Pharmacy

Abstract

Matrix metalloproteinases (MMPs) are a subfamily of zinc-dependent proteases that are re-sponsible for degradation and remodeling of extracellular matrix proteins. The activity of MMPs is tightly regulated at several levels including cleavage of prodomain, allosteric activation, com-partmentalization and complex formation with tissue inhibitor of metalloproteinases (TIMPs). In the central nervous system (CNS), MMPs play a wide variety of roles ranging from brain devel-opment, synaptic plasticity and repair after injury to the pathogenesis of various brain disorders. Following general discussion on the domain structure and the regulation of activity of MMPs, we emphasize their implication in various brain disorder conditions such as Alzheimer's disease, multiple sclerosis, ischemia/reperfusion and Parkinson's disease. We further highlight accumu-lating evidence that MMPs might be the culprit in Parkinson's disease (PD). Among them, MMP-3 appears to be involved in a range of pathogenesis processes in PD including neuroinflamma-tion, apoptosis and degradation of cc-synuclein and DJ-1. MMP inhibitors could represent poten-tial novel therapeutic strategies for treatments of neurodegenerative diseases.

Journal Title

Biomolecules & Therapeutics

Volume

20

Issue/Number

2

Publication Date

1-1-2012

Document Type

Review

Language

English

First Page

133

Last Page

143

WOS Identifier

WOS:000303224300001

ISSN

1976-9148

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