Abstract
Among the numerous strategies/targets for controlling infectious diseases, parasites-derived proteases receive prime attention due to their essential contribution to parasite growth and development. Parasites produce a broad array of proteases, which are required for parasite entry/invasion, modification/degradation of host proteins for their nourishment, and activation of inflammation that ensures their survival to maintain infection. Presently, extensive research is focused on unique proteases termed as “metacaspases” (MCAs) in relation to their versatile functions in plants and non-metazoans. Such unique MCAs proteases could be considered as a potential drug target against parasites due to their absence in the human host. MCAs are cysteine proteases, having Cys-His catalytic dyad present in fungi, protozoa, and plants. Studies so far indicated that MCAs are broadly associated with apoptosis-like cell death, growth, and stress regulation in different protozoa. The present review comprises the important research outcomes from our group and published literature, showing the variable properties and function of MCAs for therapeutic purpose against infectious diseases.
Highlights
Studies over the past 15 years demonstrated that the proteases are essential for the maintenance of normal physiology and play important roles in the regulation of cellular homeostasis and metabolism
In continuation of the above-mentioned reports on Plasmodium metacaspases, we find that P. falciparum MCA-2 (PfMCA-2) have Arg/Lys substrate specificity at pH 7.4 (Vandana et al, 2018)
Plasmodium proteases characterized so far are involved in hemoglobin degradation (Falcipains and Plasmepsins) (Silva et al, 1996; Shenai et al, 2000; Pandey et al, 2005), invasion (Subtilase, Plasmepsin IX & X) (Nasamu et al, 2017), egress and breakdown of RBC (SUB1 & Plasmepsin II, X), trafficking pathway (Plasmepsin V) (Russo et al, 2010), and many more, which help parasites to survive in an intra- or extracellular host environment
Summary
Studies over the past 15 years demonstrated that the proteases are essential for the maintenance of normal physiology and play important roles in the regulation of cellular homeostasis and metabolism. Unequal distribution of metacaspases between different phyla is an important paradigm to describe their multi-functionality such as their role in cell death, stress regulation, growth and development of parasite, etc.
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