Leishmania donovani sphingosine kinase 1 (LdSphK1)

Leishmania donovani sphingosine kinase 1 (LdSphK1) is a vital enzyme in the sphingolipid biosynthetic pathway of the protozoan parasite Leishmania donovani, the primary causative agent of visceral leishmaniasis (Sahasrabuddhe et al., 2008). This enzyme facilitates the conversion of sphingosine into sphingosine-1-phosphate (S1P), a signaling molecule that plays a crucial role in the parasite's life cycle, including its survival within host macrophages and its response to environmental stress (Zhang et al., 2003). Unlike mammalian sphingosine kinases, LdSphK1 possesses unique structural motifs and biochemical properties, making it an attractive target for selective pharmacological intervention (Goyal et al., 2014). Inhibition of LdSphK1 disrupts the balance of bioactive lipids, leading to an accumulation of sphingosine which induces programmed cell death in the parasite (Pawar et al., 2020). Current research focuses on identifying small molecule inhibitors, such as SKI-II and various synthetic analogs, that can specifically target LdSphK1 without affecting human sphingosine kinase isoforms (Verma et al., 2018). Such inhibitors represent a potential new class of anti-leishmanial agents to combat drug-resistant strains of the parasite.

Other names

LdSphKSphingosine kinase 1L. donovani sphingosine kinase

Inhibition of the phosphorylation of sphingosine to sphingosine-1-phosphate, resulting in the accumulation of toxic sphingosine and the depletion of survival-promoting S1P within the parasite (Pawar et al., 2020).