title: Drugging the schistosome zinc-dependent HDACs: current progress and future perspectives.
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.
authors.affiliation: Département de Biologie Structurale Intégrative, Institut de Génétique et Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UDS), CNRS, INSERM, 1, rue Laurent Fries, 67404 Illkirch Cedex, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Marek
authors.forename: Guilherme
authors.initials: G
authors.lastname: Oliveira
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Pierce
authors.forename: Manfred
authors.initials: M
authors.lastname: Jung
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sippl
authors.forename: Christophe
authors.initials: C
authors.lastname: Romier
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000871:Anthelmintics / Q000737:chemistry / Q000494:pharmacology*; D055808:Drug Discovery / Q000379:methods*; D015801:Helminth Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D058990:Molecular Targeted Therapy / Q000379:methods; D012547:Schistosoma / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D012550:Schistosoma mansoni / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D012552:Schistosomiasis / Q000188:drug therapy* / Q000469:parasitology; D016415:Sequence Alignment; D015032:Zinc / Q000378:metabolism
chemical_list: D000871:Anthelmintics; D015801:Helminth Proteins; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D015032:Zinc