Parasite Cathepsin D-Like Peptidases and Their Relevance as Therapeutic Targets

Trends Parasitol. 2016 Sep;32(9):708-723. doi: 10.1016/j.pt.2016.05.015. Epub 2016 Jun 22.

Abstract

Inhibition of aspartic cathepsin D-like peptidases (APDs) has been often discussed as an antiparasite intervention strategy. APDs have been considered as virulence factors of Trypanosoma cruzi and Leishmania spp., and have been demonstrated to have important roles in protein trafficking mechanisms of apicomplexan parasites. APDs also initiate blood digestion as components of multienzyme proteolytic complexes in malaria, platyhelminths, nematodes, and ticks. Increasing DNA and RNA sequencing data indicate that parasites express multiple APD isoenzymes of various functions that can now be specifically evaluated using new functional-genomic and biochemical tools, from which we can further assess the potential of APDs as targets for novel effective intervention strategies against parasitic diseases that still pose an alarming threat to mankind.

Keywords: aspartic peptidases; cathepsin D; hemoglobinolysis; parasites; vectors.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiparasitic Agents / pharmacology
  • Antiparasitic Agents / therapeutic use*
  • Drug Delivery Systems*
  • Enzyme Inhibitors / pharmacology
  • Parasites / enzymology*
  • Parasitic Diseases / drug therapy*
  • Parasitic Diseases / enzymology
  • Peptide Hydrolases / metabolism*
  • Protein Transport / genetics

Substances

  • Antiparasitic Agents
  • Enzyme Inhibitors
  • Peptide Hydrolases