The Expected Outcome of the Trypanosoma cruzi Proteomic Map: A Review of Its Potential Biological Applications for Drug
Chagas disease is a neglected tropical illness endemic to Latin America, and its treatment remains unsatisfactory. This disease is caused by the hemoflagellate protozoan Trypanosoma cruzi, which has a complex life cycle involving three evolutive forms in
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The Expected Outcome of the Trypanosoma cruzi Proteomic Map: A Review of Its Potential Biological Applications for Drug Target Discovery Rubem F.S. Menna-Barreto and Jonas Perales
Abstract Chagas disease is a neglected tropical illness endemic to Latin America, and its treatment remains unsatisfactory. This disease is caused by the hemoflagellate protozoan Trypanosoma cruzi, which has a complex life cycle involving three evolutive forms in both vertebrate and invertebrate hosts. Targeting metabolic pathways in the parasite for rational drug design represents a promising research field. This research area requires high performance techniques and proteomics become a powerful tool in this context. Here, we review advances in the construction of proteomic maps of the different forms of T. cruzi, emphasizing their biological applications towards the identification of alternative candidates for drug intervention.
Abbreviations 2-DE GPI LC-MS/MS MALDI-TOF PAF
Two-dimensional electrophoresis Glycosilphosphatydilinositol Liquid chromatography and tandem mass spectrometry Matrix-assisted laser desorption/ionization-time of flight Platelet-activating factor
R.F.S. Menna-Barreto Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ 21040-360, Brazil J. Perales (*) Laboratório de Toxinologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ 21040-360, Brazil e-mail: [email protected] A.L.S. Santos et al. (eds.), Proteins and Proteomics of Leishmania and Trypanosoma, Subcellular Biochemistry 74, DOI 10.1007/978-94-007-7305-9_13, © Springer Science+Business Media Dordrecht 2014
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R.F.S. Menna-Barreto and J. Perales
State of the Art
The hemoflagellate protozoan Trypanosoma cruzi is the etiological agent of Chagas disease, a neglected illness endemic to Latin America that emerges in non-endemic countries due to the globalization of immigration (Schmunis 2007). The evolution of the disease involves an acute phase, where a patent parasitemia can be detected, followed by a progressive chronic phase (Marin-Neto et al. 2009; Rassi et al. 2009). In the later phase, the disease pathogenesis involves cardiac and/or digestive alterations that are likely derived from prolonged inflammation induced by the persistent parasitemia (Rocha et al. 2007; SosaEstani et al. 2009). The current treatment for Chagas disease is based on two nitroheterocycles (nifurtimox and benznidazole) that were introduced four decades ago. These compounds are highly efficacious against the acute infection, but they also lead to substantial side effects and have limited activity against different parasite isolates and strains. The poor efficacy of these drugs during the chronic phase reinforces the need to search for novel active compounds against this disease (Urbina and Docampo 2003; Jannin and Villa 2007; Soeiro and DeCastro 2011). For this reason, the investigation of parasite-specific molecules as alternative chemotherapy targets has been extensively performed, with the aim of re
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