Parasite membrane sterols and Protein kinase B–associated pathways

Parasite membrane sterols and Protein kinase B (Akt)–associated pathways represent a dual-target mechanism primarily associated with the anti-leishmanial drug miltefosine. In protozoan parasites such as Leishmania, membrane sterols like ergosterol are critical for maintaining membrane integrity and the organization of lipid rafts (PMID: 22438746). The Protein Kinase B (Akt) pathway is a central regulator of cell survival, growth, and metabolism; its inhibition prevents the parasite from responding to growth signals and maintaining homeostatic balance (PMID: 21810459). Drugs targeting this axis disrupt the phospholipid bilayer and interfere with the phosphorylation of Akt-like proteins, which leads to a cascade of events resembling metazoan apoptosis, including DNA fragmentation and mitochondrial dysfunction (PMID: 17603271). This combined effect is particularly potent because it strikes both the structural and signaling foundations of the parasite. While effective, targeting these pathways can lead to significant side effects in humans, such as teratogenicity and gastrointestinal toxicity, due to the presence of homologous Akt pathways in host cells.

Other names

Ergosterol-Akt signaling axisAlkylphosphocholine target complexLeishmania Akt-like protein pathwayPhosphoinositide 3-kinase/Protein kinase B pathway

Inhibition of Akt/PKB phosphorylation and disruption of membrane sterol homeostasis, leading to programmed cell death.