Malaria: targeting parasite and host cell kinomes.

Details

Serval ID
serval:BIB_6A958247A330
Type
Article: article from journal or magazin.
Collection
Publications
Title
Malaria: targeting parasite and host cell kinomes.
Journal
Biochimica et Biophysica Acta
Author(s)
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.
ISSN
0006-3002 (Print)
ISSN-L
0006-3002
Publication state
Published
Issued date
03/2010
Volume
1804
Number
3
Pages
604-612
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Review
Publication Status: ppublish
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.
Keywords
Animals, Drug Delivery Systems/methods, Humans, Malaria/drug therapy, Malaria/enzymology, Plasmodium berghei/enzymology, Plasmodium falciparum/enzymology, Protein Kinase Inhibitors/chemistry, Protein Kinase Inhibitors/therapeutic use, Protein Kinases, Protozoan Proteins/antagonists & inhibitors
Pubmed
Create date
15/01/2014 13:37
Last modification date
20/01/2021 7:26
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