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Memórias do Instituto Oswaldo Cruz
Fundação Oswaldo Cruz, Fiocruz
ISSN: 1678-8060
EISSN: 1678-8060
Vol. 106, No. 7, 2011
Bioline Code: oc11165
Full paper language: English
Document type: Research Article
Document available free of charge

Memórias do Instituto Oswaldo Cruz, Vol. 106, No. 7, 2011

 en Chromatin regulation in schistosomes and histone modifying enzymes as drug targets
Pierce, Raymond John; Dubois-Abdesselem, Florence; Caby, Stéphanie; Trolet, Jacques; Lancelot, Julien; Oger, Frédérik; Bertheaume, Nicolas & Roger, Emmanuel

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.

Keywords
Schistosoma mansoni; histone modifying enzyme; histone deacetylase; inhibitor; drug target

 
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