Title:Melatonin Effects on Plasmodium Life Cycle: New Avenues for Therapeutic Approach
Volume: 6
Issue: 2
Author(s): Venkataramanujam Srinivasan, Asma H. Ahmad, Mahaneem Mohamed and Rahimah Zakaria
Affiliation:
Keywords:
Anti-malarial drugs, bright light therapy, luzindole, malaria, melatonin, Plasmodium falciparum, MELATONIN BIOSYNTHESIS, Cyclic AMP, SIGNAL TRANSDUCTION PATHWAYS, malarial parasite cell cycle
Abstract: Malaria remains a global health problem affecting more than 515 million people all over the world including
Malaysia. It is on the rise, even within unknown regions that previous to this were free of malaria. Although malaria
eradication programs carried out by vector control programs are still effective, anti-malarial drugs are also used extensively
for curtailing this disease. But resistance to the use of anti-malarial drugs is also increasing on a daily basis. With
an increased understanding of mechanisms that cause growth, differentiation and development of malarial parasites in rodents
and humans, new avenues of therapeutic approaches for controlling the growth, synchronization and development of
malarial parasites are essential. Within this context, the recent discoveries related to IP3 interconnected signalling pathways,
the release of Ca2+ from intracellular stores of Plasmodium, ubiquitin protease systems as a signalling pathway, and
melatonin influencing the growth and differentiation of malarial parasites by its effects on these signalling pathways have
opened new therapeutic avenues for arresting the growth and differentiation of malarial parasites. Indeed, the use of melatonin
antagonist, luzindole, has inhibited the melatonin’s effect on these signalling pathways and thereby has effectively
reduced the growth and differentiation of malarial parasites. As Plasmodium has effective sensors which detect the nocturnal
plasma melatonin concentrations, suppression of plasma melatonin levels with the use of bright light during the
night or by anti-melatonergic drugs and by using anti-kinase drugs will help in eradicating malaria on a global level. A
number of patients have been admitted with regards to the control and management of malarial growth. Patents related to
the discovery of serpentine receptors on Plasmodium, essential for modulating intra parasitic melatonin levels, procedures
for effective delivery of bright light to suppress plasma melatonin levels and thereby arresting the growth and elimination
of malarial parasites from the blood of the host are all cited in the paper. The purpose of the paper is to highlight the importance
of melatonin acting as a cue for Plasmodium faciparum growth and to discuss the ways of curbing the effects of
melatonin on Plasmodium growth and for arresting its life cycle, as a method of eliminating the parasite from the host.