Malaria: Targeting parasite and host cell kinomes

Christian Doerig, Abdirahman Abdi, Nicholas Bland, Sylvain Eschenlauer, Dominique Dorin-Semblat, Clare Fennell, Jean Halbert, Zoe Holland, Marie-Paule Nivez, Jean Philippe Semblat, Audrey Sicard, Luc Reininger

Research output: Contribution to journalReview ArticleResearchpeer-review

69 Citations (Scopus)

Abstract

Malaria still remains one of the deadliest infectious diseases, and has a tremendous morbidity and mortality impact in the developing world. The propensity of the parasites to develop drug resistance, and the relative reluctance of the pharmaceutical industry to invest massively in the developments of drugs that would offer only limited marketing prospects, are major issues in antimalarial drug discovery. Protein kinases (PKs) have become a major family of targets for drug discovery research in a number of disease contexts, which has generated considerable resources such as kinase-directed libraries and high throughput kinase inhibition assays. The phylogenetic distance between malaria parasites and their human host translates into important divergences in their respective kinomes, and most Plasmodium kinases display atypical properties (as compared to mammalian PKs) that can be exploited towards selective inhibition. Here, we discuss the taxon-specific kinases possessed by malaria parasites, and give an overview of target PKs that have been validated by reverse genetics, either in the human malaria parasite Plasmodium falciparum or in the rodent model Plasmodium berghei. We also briefly allude to the possibility of attacking Plasmodium through the inhibition of human PKs that are required for survival of this obligatory intracellular parasite, and which are targets for other human diseases.

Original languageEnglish
Pages (from-to)604-612
Number of pages9
JournalBBA Proteins and Proteomics
Volume1804
Issue number3
DOIs
Publication statusPublished - Mar 2010
Externally publishedYes

Keywords

  • Malaria
  • Plasmodium berghei
  • Plasmodium falciparum
  • Protein kinase
  • Target validation
  • Transfection
  • Transgenesis

Cite this

Doerig, C., Abdi, A., Bland, N., Eschenlauer, S., Dorin-Semblat, D., Fennell, C., Halbert, J., Holland, Z., Nivez, M-P., Semblat, J. P., Sicard, A., & Reininger, L. (2010). Malaria: Targeting parasite and host cell kinomes. BBA Proteins and Proteomics, 1804(3), 604-612. https://doi.org/10.1016/j.bbapap.2009.10.009