title: Chromatin regulation in schistosomes and histone modifying enzymes as drug targets.
abstract: Only one drug is currently available for the treatment and control of schistosomiasis and the increasing risk of selecting strains of schistosome that are resistant to praziquantel means that the development of new drugs is urgent. With this objective we have chosen to target the enzymes modifying histones and in particular the histone acetyltransferases and histone deacetylases (HDAC). Inhibitors of HDACs (HDACi) are under intense study as potential anti-cancer drugs and act via the induction of cell cycle arrest and/or apoptosis. Schistosomes like other parasites can be considered as similar to tumours in that they maintain an intense metabolic activity and rate of cell division that is outside the control of the host. We have shown that HDACi can induce apoptosis and death of schistosomes maintained in culture and have set up a consortium (Schistosome Epigenetics: Targets, Regulation, New Drugs) funded by the European Commission with the aim of developing inhibitors specific for schistosome histone modifying enzymes as novel lead compounds for drug development.
authors: Institut Pasteur de Lille, France. raymond.pierce@pasteur-lille.fr
authors: Raymond John
authors: RJ
authors: Pierce
authors: Florence
authors: F
authors: Dubois-Abdesselem
authors: Stéphanie
authors: S
authors: Caby
authors: Jacques
authors: J
authors: Trolet
authors: Julien
authors: J
authors: Lancelot
authors: Frédérik
authors: F
authors: Oger
authors: Nicolas
authors: N
authors: Bertheaume
authors: Emmanuel
authors: E
authors: Roger
mesh_terms: D000818:Animals; D002843:Chromatin / Q000187:drug effects* / Q000378:metabolism; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism*; D012547:Schistosoma / Q000187:drug effects* / Q000201:enzymology
chemical_list: D002843:Chromatin; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases