Function of Glycosomes in the Metabolism of Trypanosomatid Parasites and the Promise of Glycosomal Proteins as Drug Targets

Melisa Gualdrón-López, Paul A.M. Michels*, Wilfredo Quiñones, Ana J. Cáceres, Luisana Avilán, Juan Luis Concepción

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Trypanosomatids have the unique feature of compartmentalizing the major part of the glycolytic pathway inside peroxisome-related organelles called glycosomes. However, these organelles also contain enzymes of several other important pathways involved in both catabolic and anabolic processes. The enzyme content and the metabolic role of glycosomes differ between trypanosomatid species and between their life cycle stages. Several of the glycosomal pathways have been shown to be important for the viability, pathogenicity, and/or virulence of different trypanosomatid parasites. Additionally, the correct compartmentalization of glycosomal enzymes inside the organelles appeared to be vital for these pathogens. Therefore, many of these enzymes, as well as the proteins involved in the translocation of metabolites across the glycosomal membrane and peroxins (PEXs), proteins responsible for the biogenesis of glycosomes, are candidate drug targets. Glycosomal enzymes and PEX proteins of Trypanosoma brucei, T. cruzi, and Leishmania spp. are being studied, and compounds that interfere with their functioning are being developed for use as lead drugs against the diseases caused by these parasites. Potent, selective inhibitors of several enzymes have been obtained that exert trypanocidal activity on parasites cultured in vitro and have no or only little effect on growth of human cells. In addition, some compounds showed anti-parasite activity in experimentally infected animals.

Original languageEnglish
Title of host publicationTrypanosomatid Diseases
Subtitle of host publicationMolecular Routes to Drug Discovery
EditorsTimo Jaeger, Oliver Koch, Leopold Flohe
PublisherWiley-VCH
Chapter7
Pages121-151
Number of pages31
ISBN (Electronic)9783527670406
ISBN (Print)9783527332557
DOIs
Publication statusPublished - 4 Apr 2013

Publication series

NameDrug Discovery in Infectious Diseases
PublisherWiley-Blackwell

Keywords

  • Drug targets
  • Enzyme inhibitor
  • Glycosome
  • Life cycle
  • Peroxin
  • Trypanosomatid parasite

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