Abstract
Schistosomes, like many eukaryotic pathogens, typically display morphologically distinct stages during their life cycles. Epigenetic mechanisms underlie the pathogens’ morphological transformations, and the targeting of epigenetics-driven cellular programs therefore represents an Achilles’ heel of parasites. To speed up the search for new antiparasitic agents, drugs validated for other diseases can be rationally optimized into antiparasitic therapeutics. Specifically, zinc-dependent histone deacetylases (HDACs) are the most explored targets for epigenetic therapies, notably for anticancer treatments. This review focuses on the development of drug-leads inhibiting HDACs from schistosomes. More precisely, current progress on Schistosoma mansoni HDAC8 (smHDAC8) provided a proof of concept that targeting epigenetic enzymes is a valid approach to treat diseases caused by schistosomes, and possibly other eukaryotic pathogens.
Financial & competing interests disclosure
This work and the authors of this manuscript have been supported by funding from the European Union's Seventh Framework Program for research, technological development and demonstration under grant agreements no's. 241865 (SEtTReND) and 602080 (A-ParaDDisE). C.R., M.M. and R.J.P. are supported by institutional funds from the Centre National de la Recherche Scientifique (CNRS), the Institut National de la Santé et de la Recherche Médicale (INSERM), the Université de Strasbourg and the Université de Lille 2, the French Infrastructure for Integrated Structural Biology (FRISBI; ANR-10-INSB-05–01) and by Instruct as part of the European Strategy Forum on Research Infrastructures (ESFRI). The hHDAC8 research of M.J. (JU 295/13–1) and W.S. (SI 868/13–1) is funded by the Deutsche Forschungsgemeinschaft (DFG). G.O. is supported by CNPq (309312/2012–4, 403049/20121) and FAPEMIG (PPM-00439–10). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.