Study of branched chain amino acids metabolism in Trypanosoma cruzi: a possible therapeutic target

• Grant number: 12/19724-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2013
• End date: July 31, 2015
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Ariel Mariano Silber
• Grantee: Ludmila Nakamura Rapado
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

American trypanosomiasis (Chagas disease) is a neglected disease with about 12 million people chronically infected and more than 40 million at risk of infection. Nowadays the few drugs available to treat the disease are limited in efficacy and tolerance, which highlights the need for new therapeutic targets to development of effective drugs for treatment. Studies have described the importance of the amino acids in T. cruzi life cycle which in addition to acting in protein synthesis and energy metabolism are related to different functions in the parasite. Although previous studies indicate the branched chain amino acids (BCAA - leucine, isoleucine and valine) as part of metabolism in T. cruzi is curious that there are few studies on the identification of relevant functions of BCAA to the parasite biology, as well as other amino acids associated with the T. cruzi. This project has the purpose of: (1) Evaluate the transport of BCAA in T. cruzi. (2) Biochemically characterize of acyl-CoA dehydrogenase enzyme on BCAA pathway. (3) To evaluate the functional role of this enzyme in parasite biology. (4) Search for specific inhibitors of this enzyme. (5) Assess their possible effects related to the therapeutic potential. (6) Confirm the possible role of the leucine and isoleucine as modulators of differentiation processes proline dependent.