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DRUGGING THE SCHISTOSOME ZINC-DEPENDENT HDACS: CURRENT PROGRESS AND FUTURE PERSPECTIVES.
Helminth Proteins/antagonists & inhibitors
Schistosoma/drug effects
Autor
Afiliación
Université de Strasbourg . Institut de Génétique et Biologie Moléculaire et Cellulaire. Département de Biologie Structurale Intégrative. Lille Cedex, France
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Grupo de Genomica e Biologia Computacional. Belo Horizonte, MG, Brasil
Université de Lille. Institut Pasteur de Lille.Center for Infection & Immunity of Lille.Lille Cedex, France
Albert-Ludwigs-Universität Freiburg.Institute of Pharmaceutical Sciences. Freiburg, Germany
Martin-Luther-Universität Halle-Wittenberg. Institute of Pharmacy. Wolfgang-Langenbeck, Germany
Université de Strasbourg . Institut de Génétique et Biologie Moléculaire et Cellulaire. Département de Biologie Structurale Intégrative. Lille Cedex, France
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Grupo de Genomica e Biologia Computacional. Belo Horizonte, MG, Brasil
Université de Lille. Institut Pasteur de Lille.Center for Infection & Immunity of Lille.Lille Cedex, France
Albert-Ludwigs-Universität Freiburg.Institute of Pharmaceutical Sciences. Freiburg, Germany
Martin-Luther-Universität Halle-Wittenberg. Institute of Pharmacy. Wolfgang-Langenbeck, Germany
Université de Strasbourg . Institut de Génétique et Biologie Moléculaire et Cellulaire. Département de Biologie Structurale Intégrative. Lille Cedex, France
Resumen en ingles
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
Palabras clave en ingles
Anthelmintics/chemistryHelminth Proteins/antagonists & inhibitors
Schistosoma/drug effects
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