Synthetic and natural protease inhibitors provide insights into parasite development, virulence and pathogenesis

Curr Med Chem. 2013;20(25):3078-102. doi: 10.2174/0929867311320250005.

Abstract

Protease function is essential to many biological systems and processes. In parasites, proteases are essential for host tissue degradation, immune evasion, and nutrition acquisition. Helminths (worms) depend on several classes of proteases for development, host tissue invasion and migration, and for degradation of host hemoglobin and serum proteins. The protozoa, which cause malaria, depend on both cysteine and aspartic proteases to initiate host hemoglobin digestion. Other types of proteases are involved in erythrocyte cell invasion and cell exit. Surface metalloproteases in kinetoplastids are implicated in the evasion of complement-mediated cell lysis and cell entry. Cysteine proteases in Entamoeba facilitate invasion of the host colon. Giardia utilizes a cysteine protease for both encystation and excystation. This review will summarize published data using protease inhibitors as tools to identify the function of parasite proteases in the development, virulence, and pathogenesis of parasites; as well as the role of endogenous parasite protease inhibitors in regulation.

Publication types

  • Review

MeSH terms

  • Aminopeptidases / antagonists & inhibitors
  • Aminopeptidases / metabolism
  • Animals
  • Cestoda / enzymology
  • Cestoda / growth & development
  • Cestoda / pathogenicity
  • Cystatins / pharmacology
  • Cysteine Proteases / chemistry
  • Cysteine Proteases / metabolism
  • Helminth Proteins / antagonists & inhibitors*
  • Helminth Proteins / metabolism
  • Helminths / drug effects
  • Helminths / enzymology
  • Helminths / pathogenicity*
  • Humans
  • Nematoda / enzymology
  • Nematoda / growth & development
  • Nematoda / pathogenicity
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / pharmacology
  • Serpins / pharmacology
  • Trematoda / enzymology
  • Trematoda / growth & development
  • Trematoda / pathogenicity
  • Virulence / drug effects

Substances

  • Cystatins
  • Helminth Proteins
  • Protease Inhibitors
  • Serpins
  • Cysteine Proteases
  • Aminopeptidases