Abstract
Parasitic protozoa comprise several species that are causative agents of important diseases. These diseases are distributed throughout the world and include leishmaniasis, Chagas disease and sleeping sickness, malaria and toxoplasmosis. Treatment is based on drugs that were developed many years ago, which have side effects and produce resistant parasites. One approach for the development of new drugs is the identification of new molecular targets. We summarize the data on histone deacetylases, a class of enzymes that act on histones, which are closely associated with DNA and its regulation. These enzymes may constitute new targets for the development of antiparasitic protozoa drugs. Although several protozoan species are mentioned, members of the Trypanosomatidae family are the main focus of this short review.
Highlights
Histone deacetylases as targets for antitrypanosomal drugsParasitic protozoa comprise several species that are causative agents of important diseases
Histone deacetylases are involved in distinct cellular processes, such as gene expression control and cell death mechanisms
Epigenetic regulation has been explored in chemotherapeutic studies and for drug design as a promising alternative, including against pathogenic parasites
Summary
Parasitic protozoa comprise several species that are causative agents of important diseases. We summarize the data on histone deacetylases, a class of enzymes that act on histones, which are closely associated with DNA and its regulation These enzymes may constitute new targets for the development of antiparasitic protozoa drugs. Trypanosomatids present another DNA compartment that is important: the kDNA, which is called the kinetoplast-DNA network It is located in one specific portion of a unique single mitochondrion just below the basal bodies, from where the single flagellum emerges. The histones of the octamer present two domains: the C-terminal domain, which is found inside the nucleosome, and the N-terminal domain, which is located outside of this structure [9,11] Another important histone characteristic is that these proteins are subject to post-translational modifications (PTMs), which control gene expression, chromatin assembly, DNA replication, transcription and repair [3,9,10]
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