[Schistosoma mansoni receptor tyrosine kinases: towards new therapeutic targets].
In spite of numerous efforts towards the control of its transmission, schistosomiasis still remains an important parasitic disease and represents a serious public health concern and a major economical problem in a lot of developing countries. The detection in different S. mansoni endemic areas of resistance to Praziquantel, the only drug currently used against the parasite, was sufficient to motivate actively further research for the discovery of novel drug treatments. Specific inhibitors for tyrosine kinase receptors (such as EGF receptor) are currently used with success as anti-tumor drugs. As cell proliferation and differentiation are essential events in the complex life cycle of the schistosome, we have attempted to consider parasite growth factor receptors as potential targets for a new generation of anti-parasitic agents. Three RTK have been identified in S. mansoni: an EGF receptor, an insulin receptor and a third receptor with an original structure probably belonging to a new class of RTK never identified. Structural and functional analyses of the parasite receptors demonstrated the conservation but also the divergences with their vertebrate counterparts, which are therefore excellent candidates for strategies of specific parasite RTK inhibition.
U547 INSERM, Institut Pasteur de Lille, 1, rue du Pr Calmette, 59019 Lille Cedex.
Jérôme
J
Vicogne
Colette
C
Dissous
D000818:Animals; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015801:Helminth Proteins / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000145:classification / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology; D012550:Schistosoma mansoni / Q000187:drug effects / Q000201:enzymology*; D012555:Schistosomiasis mansoni / Q000188:drug therapy / Q000469:parasitology; D012556:Schistosomicides / Q000494:pharmacology*; D014612:Vaccines
D004791:Enzyme Inhibitors; D015801:Helminth Proteins; D007328:Insulin; D012556:Schistosomicides; D014612:Vaccines; D020794:Receptor Protein-Tyrosine Kinases; C486192:SER receptor, Schistosoma mansoni; C486194:SmRTK-1, Schistosoma mansoni; C486195:SmRTK-2, Schistosoma mansoni