Enolase (Naegleria fowleri) (NfENO)

Enolase from Naegleria fowleri (NfENO) is a critical glycolytic enzyme that catalyzes the reversible dehydration of 2-phospho-D-glycerate to phosphoenolpyruvate. In the pathogenic trophozoite stage of N. fowleri, the organism is highly dependent on glycolysis for energy production and growth, making this enzyme a vulnerable metabolic node. NfENO has recently gained attention as a potential therapeutic target for Primary Amoebic Meningoencephalitis (PAM), a rare but nearly always fatal brain infection caused by this "brain-eating" amoeba. Experimental phosphonate inhibitors, such as HEX, which were originally designed to target human enolase 2 in certain cancers, have shown potent amoebicidal activity by blocking NfENO and disrupting the parasite's energy metabolism. While these inhibitors have demonstrated the ability to extend survival in animal models of infection, challenges remain regarding drug delivery across the blood-brain barrier and ensuring sufficient selectivity to avoid inhibiting essential human enolase isoforms.

Other names

Phosphopyruvate hydratase2-phospho-D-glycerate hydro-lyaseNfEnolase

Inhibition of the enolase enzyme, which prevents the conversion of 2-phosphoglycerate to phosphoenolpyruvate, thereby disrupting the glycolytic pathway and depleting the amoeba of energy (ATP).