From proteins to molecular targets: Trypanosoma cruzi proteomic insights in drug development
Giselle V-F Brunoro, Marcelle A Caminha and Rubem FS Menna-Barreto
from: Protozoan Parasitism: From Omics to Prevention and Control (Edited by: Luis Miguel de Pablos Torró and Jacob-Lorenzo Morales). Caister Academic Press, U.K. (2018) Pages: 1-30.
Chagas disease is a neglected disease caused by the hemoflagellate protozoan Trypanosoma cruzi, which is endemic to Latin America, that emerges in non-endemic areas due to immigration. The parasite presents a complex life cycle, including two hosts (invertebrate and vertebrate) and three developmental stages (epimastigotes, trypomastigotes and amastigotes). The current chemotherapy is restricted to two nitroheterocycles, nifurtimox and benznidazole, which present limited efficacy depending on the disease phase. Multidisciplinary efforts have been made to identify promising novel parasite-specific key molecules to develop nitroderivative substitutes, increase trypanocidal activity and minimize host toxicity. In this context, deep analysis of drug pharmacokinetics and mechanisms of action is crucial to improve specificity and safety. We reviewed proteomics as a valuable tool for the identification of molecular targets of T. cruzi. Advances in parasite proteomic maps (different developmental stages and strains) were reviewed, emphasizing the promising targets, their biological applications, and possible follow-up analysis for the development of novel anti-T. cruzi drugs read more ...