Molecular and Cellular Pharmacology, Vol 4, No 3 (2012)

Apicomplexan Cyclophilins in Host-parasite Interaction and Their Potential as Anti-parasitic Drug Targets

Abstract

The Apicomplexa consist of numerous genera of pathogenic protozoa, many of which cause diseases in humans and in economically important animal species. Cyclophilins exhibit peptidyl-prolyl cis-trans isomerase activity that plays a vital role in protein folding. Immunophilins such as cyclophilins and FK506-binding proteins are not only involved in the folding, trafficking and activity of a range of cellular proteins, but also mediate the effects of certain pharmacologically active small molecules. Apart from their roles in cellular biochemistry, immunophilins of parasites are particularly interesting for two additional reasons. First, there is evidence that some are involved in the pathogenesis of infections caused by protozoa and other microorganisms. Second, cyclophilins are sensitive to cyclosporin A (CsA), which has strong inhibitory effects on certain parasites in culture and in animal models of infection. This review considers the properties of cyclophilins, focusing on their roles in host-parasite interaction and their potential as anti-parasitic drug targets. Cyclophilins of Toxoplasma and Neospora can manipulate the immune response through sophisticated mechanisms that are able to instruct and subvert host cell responses. This dual capability of the parasite could mediate the establishment of a stable host-parasite interaction. Moreover, cyclophilins of malarial parasites have particular interest as potent and selective anti-parasitic drug targets. The discovery that CsA anti-parasitic effect and inhibitory activity against a wide variety of Apicomplexa cyclophilins has focused attention on cyclophilins as valuable targets for new drugs against this important group of pathogens.

Keywords: Apicomplexa; Cyclophilins; Host-parasite interaction; Cyclosporin A; Immunophilins; Anti-parasitic drug targets.

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