The multiple sclerosis degradome: Enzymatic cascades in development and progression of central nervous system inflammatory disease

Research output: Chapter in Book/Report/Conference proceedingChapter

32 Scopus citations

Abstract

An array of studies implicate different classes of protease and their endogenous inhibitors in multiple sclerosis (MS) pathogenesis based on expression patterns in MS lesions, sera, and/or cerebrospinal fluid (CSF). Growing evidence exists regarding their mechanistic roles in inflammatory and neurodegenerative aspects of this disease. Proteolytic events participate in demyelination, axon injury, apoptosis, and development of the inflammatory response including immune cell activation and extravasation, cytokine and chemokine activation/inactivation, complement activation, and epitope spreading. The potential significance of proteolytic activity to MS therefore relates not only to their potential use as important biomarkers of disease activity, but additionally as prospective therapeutic targets. Experimental data indicate that understanding the net physiological consequence of altered protease levels in MS development and progression necessitates understanding protease activity in the context of substrates, endogenous inhibitors, and proteolytic cascade interactions, which together make up the MS degradome. This review will focus on evidence regarding the potential physiologic role of those protease families already identified as markers of disease activity in MS; that is, the metallo-, serine, and cysteine proteases.

Original languageEnglish (US)
Title of host publicationAdvances in multiple Sclerosis and Experimental Demyelinating Diseases
PublisherSpringer Verlag
Pages133-175
Number of pages43
ISBN (Print)9783540736769
DOIs
StatePublished - 2008

Publication series

NameCurrent Topics in Microbiology and Immunology
Volume318
ISSN (Print)0070-217X

ASJC Scopus subject areas

  • Immunology and Allergy
  • Microbiology
  • Immunology
  • Microbiology (medical)

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