Expression of cysteine proteinases and cystatins in parasites and use of cysteine proteinase inhibitors in parasitic diseases. Part III: Protozoa (2): Plasmodium spp. | ||||
| Parasitologists United Journal | ||||
| Article 1, Volume 12, Issue 2, August 2019, Page 72-93 PDF (440.12 K) | ||||
| Document Type: Review Article | ||||
| DOI: 10.21608/puj.2019.14599.1049 | ||||
 View on SCiNiTO | ||||
| Author | ||||
Sherif Abaza 
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| Medical Parasitology Department, Faculty of Medicine, Suez Canal Uinversity, Ismailia, Egypt | ||||
| Abstract | ||||
| Genomic analysis of P. falciparum revealed more than thirty cysteine proteases (CPs). However, the most studied CPs are four falcipains (FPs), three dipeptidyl peptidases, a calpain and a metacaspase. Beside the main function of hemoglobin degradation, CPs are not only essential for protein trafficking, but they are also involved in egress cascade, i.e. rupture of infected erythrocytes as well as de novo RBCs invasion. In addition, studies showed their essential role in exo-erythrocytic hepatic stages, as well as oocyst production and gamete egress in mosquitoes. Accordingly, CPs inhibitors (CPIs) are of great interest in development of novel anti-malarial drugs as well as a new strategy to eliminate malaria transmission. Several compounds were investigated as CPIs including herbal extracts, known proteases with reported inhibitory potency against papain-like family, chemical compounds and synthesized derivatives as well as commercially available drugs approved for human use for other diseases. However, no commercial drug-targeting FPs has been developed yet. On the other hand, endogenous parasites cystatins (CYSs) regulate CPs and prevent inappropriate effects of host enzymes. The present review will discuss the role of essential plasmodial CPs and the importance of search for or development of potent specific selective CPI as a novel anti-marital drug. Hopefully the rapid development of highly efficient technology promises advances of expression systems using genetic tools for metabolic regulation of protein expression. This is in addition to recent technology for advanced screening directed with molecular modeling using three-dimensional construction of the target CP | ||||
| Keywords | ||||
| drug targets; falcipains; Malaria; plasmodial proteinases | ||||
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