Paul O. Okonkwo

Lipid Transport in Plasmodium: Role as Possible Target for Novel Chemotherapy Against Malaria

Lipid trafficking pathways in malaria-infected erythrocytes are complex because the malaria parasite is separated from the serum by the erythrocyte and parasitophorous vacuolar membrane (PVM). The PVM lipids in malaria-infected erythrocytes are derived from host cells. Lipid rafts which are cholesterol and sphingolipid enriched membrane domains appear to be involved in malaria infection. Thus, perturbation of lipid raft specific lipids in the host erythrocyte membrane can influence the cell’s ability to be infected. This paper attempts to discuss novel approaches in the treatment of malaria infection by targeting and manipulating host cell lipids based on recent discoveries on the role of lipid rafts in malaria pathogenesis.

Role of Tumour Necrosis Factor (TNF) and Glycosylphosphatidylinositol (GPI) as Important Mediators in the Pathogenesis of Malaria Infection

It has been shown from circumstantial and direct evidence that excess production of Tumour Necrosis Factor (TNF) in response to parasite toxins contribute to severe pathology and death in malaria infection. A study demonstrated that glycosylphosphatidylinositol (GPI) moieties covalently linked to the surface antigens of malaria parasites have the properties of such toxins, as the highly purified GPIs free of associated proteins are able to induce high levels of TNF and IL-1 from macrophages to cause pyrexia and cachexia in vivo. The GPI molecules linked to surface antigens of the parasite glycolipid toxins elicit several pathophysiological responses associated with acute severe malaria. This paper aims to review the effects of GPIs and TNF as mediators of pro-inflammatory and immunological mechanisms in the pathogenesis of malaria.

Lipid Metabolism in Plasmodium: Implication as Possible Target for Chemotherapy

Lipid metabolism of the parasite is associated with alterations in fatty acids and cholesterol in the erythrocyte plasma membrane, which in turn are responsible for changes in permeability and fragility. The augmentation of all the membrane systems of the infected erythrocyte causes the lipid content to rise rapidly, but the parasite lipid composition differs from that of the erythrocyte in many respects. Phospholipid metabolism has been identified as an ideal target for novel anti-malarial chemotherapy due to its vital importance to the parasite. This paper attempts to review the underlying lipid metabolic pathways in the malaria parasite and their potential benefit as likely targets for novel anti-malarial chemotherapy.