Abstract
Cysteine proteases (CPs) play key roles in the pathogenesis of protozoan parasites, including cell/tissue penetration, hydrolysis of host or parasite proteins, autophagy, and evasion or modulation of the host immune response, making them attractive chemotherapeutic and vaccine targets. This review highlights current knowledge on clan CA cysteine proteases, the best-characterized group of cysteine proteases, from 7 protozoan organisms causing human diseases with significant impact: Entamoeba histolytica, Leishmania species (sp.), Trypanosoma brucei, T. cruzi, Cryptosporidium sp., Plasmodium sp., and Toxoplasma gondii. Clan CA proteases from three organisms (T. brucei, T. cruzi, and Plasmodium sp.) are well characterized as druggable targets based on in vitro and in vivo models. A number of candidate inhibitors are under development. CPs from these organisms and from other protozoan parasites should be further characterized to improve our understanding of their biological functions and identify novel targets for chemotherapy.
Highlights
Proteases are enzymes that catalyze the hydrolysis of peptide bonds and are important in a number of biological activities, including digestion of peptides, activation of other enzymes, modulation of the immune system, participation in the cell cycle, and differentiation and autophagy
Cysteine proteases (CPs) are categorized into 72 families, but not all are represented in protozoan parasites [1]
L. mexicana CPs cleave JNK and ERK MAP kinases. Both kinases negatively regulate IL-12 production, and the protozoan cysteine protease CPB can alter host macrophage signaling by increasing IL-12 transcription [35]
Summary
This review highlights current knowledge on clan CA cysteine proteases, the best-characterized group of cysteine proteases, from 7 protozoan organisms causing human diseases with significant impact: Entamoeba histolytica, Leishmania species (sp.), Trypanosoma brucei, T. cruzi, Cryptosporidium sp., Plasmodium sp., and Toxoplasma gondii.
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