Glutathione redox system as a therapeutic target for Plasmodium: Opportunities, Challenges, and future perspectives

Glutathione (GSH) serves as an essential guardian for parasites, protecting them from the onslaught of oxidative stress. As hemoglobin breaks down and energy is harvested through the intricate mitochondrial respiratory pathway, GSH meticulously creates a reducing environment, akin to a fortress against oxidative damage. The metabolic pathways involving GSH in parasites are complex and markedly different from those in human hosts, rendering them a compelling target in the battle against multidrug-resistant parasites. This review illuminates the critical role of GSH in the survival of malaria parasites and the impact of key enzyme inhibitors on the GSH redox pathway. Recent discoveries surrounding significant enzyme inhibitors as GST, GR, GS, and GP, are explored, shedding light on the potential of combination therapies while underscoring the obstacles posed by selective drug targeting and the imperative to navigate drug resistance. Moreover, the review delves into the forefront of research on the metabolic pathways of GSH in parasites, unveiling a trove of promising drug targets for strategies aimed at treating malaria in an era plagued by multidrug resistance and offers hope for innovative therapeutic approaches against one of the world's most persistent diseases.