Microglial functions and proteases

Hiroshi Nakanishi

Research output: Contribution to journalReview article

121 Citations (Scopus)

Abstract

There is accumulating evidence that intracellular and extracellular proteases of microglia contribute to various events in the central nervous system (CNS) through both nonspecific and limited proteolysis. Cathepsin E and cathepsin S, endosomal/lysosomal proteases, have been shown to play important roles in the major histocompatibility complex (MHC) class II-mediated antigen presentation of microglia by processing of exogenous antigens and degradation of the invariant chain associated with MHC class II molecules, respectively. Some members of cathepsins are also involved in neuronal death after secreted from microglia and clearance of phagocytosed amyloid-β peptides. Tissue-type plasminogen activator, a serine protease, secreted from microglia participates in neuronal death, enhancement of N-methyl-D-aspartate receptor-mediated neuronal responses, and activation of microglia via either proteolytic or nonproteolytic activity. Calpain, a calcium-dependent cysteine protease, has been shown to play a pivotal role in the pathogenesis of multiple sclerosis by degrading myelin proteins extracellulary. Furthermore, matrix metalloproteases secreted from microglia also receive great attention as mediators of inflammation and tissue degradation through processing of pro-inflammatory cytokines and damage to the blood-brain barrier. The growing knowledge about proteolytic events mediated by microglial proteases will not only contribute to better understanding of microglial functions in the CNS but also may aid in the development of protease inhibitors as novel neuroprotective agents.

Original languageEnglish
Pages (from-to)163-176
Number of pages14
JournalMolecular Neurobiology
Volume27
Issue number2
DOIs
Publication statusPublished - Apr 1 2003

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Microglia
Peptide Hydrolases
cathepsin S
Antigen Presentation
Major Histocompatibility Complex
Cathepsin E
Central Nervous System
Myelin Proteins
Cathepsins
Inflammation Mediators
Calpain
Cysteine Proteases
Histocompatibility Antigens Class II
Metalloproteases
Serine Proteases
Neuroprotective Agents
Tissue Plasminogen Activator
Protease Inhibitors
N-Methyl-D-Aspartate Receptors
Blood-Brain Barrier

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

Cite this

Microglial functions and proteases. / Nakanishi, Hiroshi.

In: Molecular Neurobiology, Vol. 27, No. 2, 01.04.2003, p. 163-176.

Research output: Contribution to journalReview article

Nakanishi, Hiroshi. / Microglial functions and proteases. In: Molecular Neurobiology. 2003 ; Vol. 27, No. 2. pp. 163-176.
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