2013
DOI: 10.2174/0929867311320250010
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Calpains: Potential Targets for Alternative Chemotherapeutic Intervention Against Human Pathogenic Trypanosomatids

Abstract: 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 chang… Show more

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Cited by 40 publications
(64 citation statements)
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“…Many experimental evidences have demonstrated the important roles that calpain-like proteins (CALPs) may play in trypanosomatids, such as the stage-specific expression in distinct parasites and the differential expression of CALPs in drug-resistant strains (Branquinha et al 2013). Calpains are neutral, calcium-dependent cysteine peptidases that form one of the most important proteolytic systems of mammalian cells (Goll et al 2003, Ono & Sorimachi 2012).…”
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confidence: 99%
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“…Many experimental evidences have demonstrated the important roles that calpain-like proteins (CALPs) may play in trypanosomatids, such as the stage-specific expression in distinct parasites and the differential expression of CALPs in drug-resistant strains (Branquinha et al 2013). Calpains are neutral, calcium-dependent cysteine peptidases that form one of the most important proteolytic systems of mammalian cells (Goll et al 2003, Ono & Sorimachi 2012).…”
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confidence: 99%
“…Numerous functions related to signal transduction, cell motility, differentiation, proliferation, gene expression and apoptosis have been postulated for calpains in the human body (Goll et al 2003, Ono & Sorimachi 2012). The large and diverse family of CALPs detected in trypanosomatids (Ersfeld et al 2005) was categorised into five groups, based on their structural features, but the absence of amino acid residues essential for catalytic activity and the moderate overall degree of sequence identity with human calpains suggest that most of these CALPs do not have proteolytic activity (Ersfeld et al 2005, Branquinha et al 2013). Non-proteolytic CALPs are likely to function as structural elements and in regulatory processes, and as such a universal function of calpains and CALPs appears to be that of a scaffold by interacting with various molecules, as shown by their wide range of substrate specificity (Tonami et al 2007).…”
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“…Given the key role of peptidases in biological systems, these enzymes have been considered a potential therapeutic target against infectious agents 17,18 . Different classes of peptidases participate in important biological events in the T. cruzi life cycle, including processes of invasion, differentiation, proliferation as well as mechanisms of escape from host immune responses 19 .…”
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confidence: 99%