Role of proteases during intra-erythrocytic developmental cycle of human malaria parasite Plasmodium falciparum

Abstract

Malaria remains a major parasitic disease in the tropical and sub-tropical countries mainly due to dramatic increase in parasite lines resistant to commonly used anti-malarials. Characterization of novel metabolic pathways in the parasites and understanding their functional role is a prerequisite to design new anti-malarial strategies. Parasite proteases play key role in growth and differentiation of all the developmental stages across the parasite life cycle and present the most promising targets to develop new drugs against malaria. In Plasmodium falciparum genome database a total of 123 proteases are identifi ed; these proteases belong to fi ve different clans: Cysteine, Aspartic, Serine, Metallo-, and Threonine. Some of the most studied parasite proteases are those that are functional in the asexual blood stage cycle. Starting with the processing of key parasite ligand in merozoite, the invasive form of blood stage parasite, degradation of host hemoglobin in food-vacuole, regulation of levels of key metabolic pathways in cytosol and cellular organelles, degradation of misfolded and unused proteins, and rupture of host membrane for egress of daughter merozoites is mediated by these proteases. Here we discuss roles of some of the parasite proteases involved in various steps of the parasite intraerythrocytic cycle.