title: Cruzipain: An Update on its Potential as Chemotherapy Target against the Human Pathogen Trypanosoma cruzi.
abstract: Chagas' disease is one of the most impactful and prevalent neglected tropical diseases in the Americas, specially affecting the poor and underdeveloped areas in Latin America. Aggravating this scenario, the medicines used in the current chemotherapy are old, toxic and present a low efficacy to treat the chronic stage of this disease. In addition, resistant strains of Trypanosoma cruzi, the etiological agent, are frequently reported. So, there is an imperative requirement for novel chemotherapeutic options to treat this debilitating disease. In this context, peptidases have emerged as potential targets and, consequently, proteolytic inhibitors have confirmed to be valuable drugs against several human pathologies. In this line of thinking, T. cruzi produces a major multifunctional cysteine peptidase, named cruzipain, which directly and/or indirectly orchestrates several physiological and pathological processes, which culminate in a successful parasitic infection. Taken together, these findings point out that cruzipain is one of the most important targets for driving a chemotherapy approach against the human pathogen T. cruzi. The present review summarizes some of the recent advances and failures in this area, with particular emphasis on recently published studies.
authors.affiliation: Laboratorio de Investigacao de Peptidases (LIP), Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes (IMPG), Centro de Ciencias da Saude (CCS), Universidade Federal do Rio de Janeiro (UFRJ), Bloco E-subsolo, Sala 05, Av. Carlos Chagas Filho 373, 21941-902, Rio de Janeiro, Brazil. mbranquinha@micro.ufrj.br.
authors.forename: M H
authors.initials: MH
authors.lastname: Branquinha
authors.forename: S S C
authors.initials: SS
authors.lastname: Oliveira
authors.forename: L S
authors.initials: LS
authors.lastname: Sangenito
authors.forename: C L
authors.initials: CL
authors.lastname: Sodre
authors.forename: L F
authors.initials: LF
authors.lastname: Kneipp
authors.forename: C M
authors.initials: CM
authors.lastname: d'Avila-Levy
authors.forename: A L S
authors.initials: AL
authors.lastname: Santos
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology*; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000494:pharmacology*; D008968:Molecular Conformation; D021261:Parasitic Sensitivity Tests; D015800:Protozoan Proteins; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D000981:Antiprotozoal Agents; D015800:Protozoan Proteins; D003546:Cysteine Endopeptidases; C063214:cruzipain