Abstract
The cyclic nucleotides 3′, 5′-cyclic adenosine monophosphate (cAMP) and 3′, 5′-cyclic guanosine monophosphate (cGMP) are intracellular messengers found in most animal cell types. They usually mediate an extracellular stimulus to drive a change in cell function through activation of their respective cyclic nucleotide-dependent protein kinases, PKA and PKG. The enzymatic components of the malaria parasite cyclic nucleotide signalling pathways have been identified, and the genetic and biochemical studies of these enzymes carried out to date are reviewed herein. What has become very clear is that cyclic nucleotides play vital roles in controlling every stage of the complex malaria parasite life cycle. Our understanding of the involvement of cyclic nucleotide signalling in orchestrating the complex biology of malaria parasites is still in its infancy, but the recent advances in our genetic tools and the increasing interest in signalling will deliver more rapid progress in the coming years.
Highlights
Malaria parasites are fascinating organisms to study; research efforts, are primarily motivated by their devastating impact on humanity each year
Around 70% of these deaths are in children under 5 years old in Africa [1] infected with Plasmodium falciparum who have not built up sufficient natural immunity
Important steps have been made in determining the function of cyclic nucleotide signalling in malaria parasites, but recent advances in our genetic tools will ensure that we will have a more complete picture in the 5–10 years
Summary
Malaria parasites are fascinating organisms to study; research efforts, are primarily motivated by their devastating impact on humanity each year. When an infected female mosquito bites a person, sporozoites are injected into the bloodstream which travel to the liver where they invade hepatocytes They divide asexually and eventually the hepatocyte ruptures to liberate thousands of merozoites from each infected cell. Asexually by a process called schizogony whereby multiple daughter cells develop within a vacuole inside the infected erythrocyte This blood stage cycle is responsible for all the pathology associated with malaria and, in the case of P. falciparum, takes 48 h. It is clear that this complex life cycle must be tightly regulated to allow appropriate development and survival of all these highly specialized parasite forms in the varied environments they encounter This has led researchers to investigate the signalling pathways that might be responsible for coordinating the timely progression of this intricate life cycle. Functional studies of the key enzymatic components facilitate our interpretation of pharmacological studies and in some cases necessitate a re-evaluation of the data
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