Ned-19 inhibition of parasite growth and multiplication suggests a role for NAADP mediated signalling in the asexual development of Plasmodium falciparum

Pablo Suárez-Cortés, Guido Gambara, Annarita Favia, Fioretta Palombi, Pietro Alano, Antonio Filippini

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Although malaria is a preventable and curable human disease, millions of people risk to be infected by the Plasmodium parasites and to develop this illness. Therefore, there is an urgent need to identify new anti-malarial drugs. Ca2+ signalling regulates different processes in the life cycle of Plasmodium falciparum, representing a suitable target for the development of new drugs. Results: This study investigated for the first time the effect of a highly specific inhibitor of nicotinic acid adenine dinucleotide phosphate (NAADP)-induced Ca2+ release (Ned-19) on P. falciparum, revealing the inhibitory effect of this compound on the blood stage development of this parasite. Ned-19 inhibits both the transition of the parasite from the early to the late trophozoite stage and the ability of the late trophozoite to develop to the multinucleated schizont stage. In addition, Ned-19 affects spontaneous intracellular Ca2+ oscillations in ring and trophozoite stage parasites, suggesting that the observed inhibitory effects may be associated to regulation of intracellular Ca2+ levels. Conclusions: This study highlights the inhibitory effect of Ned-19 on progression of the asexual life cycle of P. falciparum. The observation that Ned-19 inhibits spontaneous Ca2+ oscillations suggests a potential role of NAADP in regulating Ca2+ signalling of P. falciparum.

Original languageEnglish
Article number366
JournalMalaria Journal
Volume16
Issue number1
DOIs
Publication statusPublished - Sep 12 2017

Keywords

  • Antimalarial drugs
  • Calcium signalling
  • Malaria
  • NAADP
  • NAADP receptor
  • Ned-19
  • P. falciparum development
  • Plasmodium falciparum

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

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