Plasmodium falciparum redox network proteins

The Plasmodium falciparum redox network proteins represent a complex array of enzymes and antioxidant molecules essential for the survival of the malaria parasite during its intraerythrocytic stage. This network primarily consists of the thioredoxin and glutathione systems, which work in tandem to maintain intracellular thiol-disulfide homeostasis and neutralize reactive oxygen species (ROS) generated by hemoglobin digestion and host immune responses (Müller et al., 2003). Key enzymes such as thioredoxin reductase (PfTrxR) and glutathione reductase (PfGR) are central to these pathways, providing the reducing equivalents necessary for DNA synthesis and the repair of oxidatively damaged proteins (Becker et al., 2004). Because the parasite lacks a catalase and has a limited repertoire of antioxidant enzymes compared to its human host, it is particularly vulnerable to oxidative stress (Jortani et al., 2020). Therapeutic strategies targeting this network often involve the use of inhibitors like methylene blue or auranofin, which disrupt the parasite's ability to manage oxidative loads, leading to rapid parasite death (Buchholz et al., 2008). However, drug development must account for the high degree of similarity between some parasite enzymes and their human counterparts to avoid off-target toxicity, particularly in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency (Sarma et al., 2003).

Other names

Plasmodium falciparum antioxidant systemPf redox metabolismThioredoxin-glutathione system of P. falciparumPlasmodium falciparum redox homeostasis proteins

Inhibition of key oxidoreductase enzymes, specifically thioredoxin reductase and glutathione reductase, to disrupt thiol-disulfide homeostasis and induce lethal oxidative stress within the parasite (Becker et al., 2004; Müller et al., 2003).