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Enzyme Research
Volume 2011, Article ID 648159, 13 pages
http://dx.doi.org/10.4061/2011/648159
Review Article

The Sphingolipid Biosynthetic Pathway Is a Potential Target for Chemotherapy against Chagas Disease

Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Bloco G-019, Cidade Universitária—Ilha do Fundão, 21941-902 Rio de Janeiro RJ, Brazil

Received 20 December 2010; Revised 17 February 2011; Accepted 25 February 2011

Academic Editor: Elena Gonzalez-Rey

Copyright © 2011 Carolina Macedo Koeller and Norton Heise. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The protozoan parasite Trypanosoma cruzi is the causative agent of human Chagas disease, for which there currently is no cure. The life cycle of T. cruzi is complex, including an extracellular phase in the triatomine insect vector and an obligatory intracellular stage inside the vertebrate host. These phases depend on a variety of surface glycosylphosphatidylinositol-(GPI-) anchored glycoconjugates that are synthesized by the parasite. Therefore, the surface expression of GPI-anchored components and the biosynthetic pathways of GPI anchors are attractive targets for new therapies for Chagas disease. We identified new drug targets for chemotherapy by taking the available genome sequence information and searching for differences in the sphingolipid biosynthetic pathways (SBPs) of mammals and T. cruzi. In this paper, we discuss the major steps of the SBP in mammals, yeast and T. cruzi, focusing on the IPC synthase and ceramide remodeling of T. cruzi as potential therapeutic targets for Chagas disease.