Glycolysis and protein translocation in glycosome as targets for trypanosomatid drug design (Review)

Abstract

Trypanosomatids cause neglected tropical diseases and the present review discussed the potential of targeting glycolysis and protein translocation within glycosomes as therapeutic strategies against these infections. Different studies show that glycolysis serves as the primary energy source for parasites such as <em>Trypanosoma cruzi</em>, <em>T. brucei </em>and <em>Leishmania</em>, with their glycolytic enzymes showing substantial divergence from human glycolytic enzymes, offering opportunities for selective drug development. Inhibiting glycolysis can lead to significant mortality among parasites, as even partial blockage of this pathway disrupts adenosine triphosphate production, which is essential for survival of the parasites. The present review also investigated the mechanisms of protein translocation across the glycosomal membrane, especially the critical role of peroxins; mislocalization of glycosomal proteins adversely affects parasite viability. Understanding the mechanisms of protein import and the unique characteristics of glycosomal enzymes can facilitate rational drug design aimed at these specific targets. Overall, the present review emphasized the need for innovative therapeutic approaches to effectively address the challenges posed by trypanosomatid diseases, advocating for further investigation into the metabolic vulnerabilities of these parasites to develop targeted and effective treatments.