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CALPAINS: POTENTIAL TARGETS FOR ALTERNATIVE CHEMOTHERAPEUTIC INTERVENTION AGAINST HUMAN PATHOGENIC TRYPANOSOMATIDS
Branquinha, M. H. et al. | Date Issued: 2013
Author
Branquinha, M. H.
Marinho, F. A.
Sangenito, L. S.
Oliveira, S. S. C.
Gonçalves, K. C.
Vidal, V. Ennes
Levy, C. M. d`Avila
Santos, A. L. S.
Affilliation
Universidade Federal do Rio de Janeiro (UFRJ). Instituto de Microbiologia Paulo de Góes (IMPG). Departamento de Microbiologia Geral. Laboratório de Investigação de Peptidases. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro (UFRJ). Instituto de Microbiologia Paulo de Góes (IMPG). Departamento de Microbiologia Geral. Laboratório de Investigação de Peptidases. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro (UFRJ). Instituto de Microbiologia Paulo de Góes (IMPG). Departamento de Microbiologia Geral. Laboratório de Investigação de Peptidases. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro (UFRJ). Instituto de Microbiologia Paulo de Góes (IMPG). Departamento de Microbiologia Geral. Laboratório de Investigação de Peptidases. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro (UFRJ). Instituto de Microbiologia Paulo de Góes (IMPG). Departamento de Microbiologia Geral. Laboratório de Investigação de Peptidases. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro (UFRJ). Instituto de Química. Programa de Pós-Graduação em Bioquímica. Rio de Janeiro, RJ, Brasil.
Abstract
The treatment for both leishmaniasis and trypanosomiasis, which are severe human infections caused by trypanosomatids belonging to Leishmania and Trypanosoma genera, respectively, is extremely limited because of concerns of toxicity and efficacy with the available anti-protozoan drugs, as well as the emergence of drug resistance. Consequently, the urgency for the discovery of new trypanosomatid targets and novel bioactive compounds is particularly necessary. In this context, the investigation of changes in parasite gene expression between drug resistant/sensitive strains and in the up-regulation of virulence-related genes in infective forms has brought to the fore the involvement of calpain-like proteins in several crucial pathophysiological processes performed by trypanosomatids. These studies were encouraged by the publication of the complete genome sequences of three human pathogenic trypanosomatids, Trypanosoma brucei, Trypanosoma cruzi and Leishmania major, which allowed in silico analyses that in turn directed the identification of numerous genes with interesting chemotherapeutic characteristics, including a large family of calpain-related proteins, in which to date 23 genes were assigned as calpains in T. brucei, 40 in T. cruzi and 33 in L. braziliensis. In the present review, we intend to add to these biochemical/biological reports the investigations performed upon the inhibitory capability of calpain inhibitors against human pathogenic trypanosomatids.
Keywords
Alternative chemotherapy
Calpain
Leishmania
Monoxenous trypanosomatids
Peptidase inhibitor
Trypanosoma
Virulence
 
DeCS
Leishmania
Calpaína
Peptidase
Leishmaniose
Trypanosoma cruzi
 
Publisher
Bentham Science Publishers
Citation
BRANQUINHA, M. H.; et al. Calpains: Potential Targets for Alternative Chemotherapeutic Intervention Against Human Pathogenic Trypanosomatids. Current Medicinal Chemistry, v.20, n.25, p.3174-3185, 2013.
ISSN
1875-533X