Matrix metalloproteinases, new insights into the understanding of neurodegenerative disorders

Yoon Seong Kim, Tong H. Joh

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

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 α-synuclein and DJ-1. MMP inhibitors could represent poten-tial novel therapeutic strategies for treatments of neurodegenerative diseases.

Original languageEnglish (US)
Pages (from-to)133-143
Number of pages11
JournalBiomolecules and Therapeutics
Volume20
Issue number2
DOIs
StatePublished - May 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery

Keywords

  • MMP-3
  • Matrix metalloproteinases
  • Microglia
  • Neurodegenerative disorders
  • Parkinson's disease

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