Parasitic histone deacetylase (HDAC)

Parasitic histone deacetylases (HDACs) are a class of enzymes found in various pathogenic parasites, including protozoa such as Plasmodium falciparum (malaria), Trypanosoma cruzi (Chagas disease), and Leishmania species, as well as helminths like Schistosoma mansoni (nih.gov). These enzymes catalyze the removal of acetyl groups from lysine residues on histones and non-histone proteins, playing a critical role in epigenetic regulation, gene expression, and cellular processes such as the cell cycle and differentiation (nih.gov, uni-halle.de). In parasites, HDACs are essential for life cycle progression and survival within the host (nih.gov). Targeting these enzymes with histone deacetylase inhibitors (HDACis) leads to the hyperacetylation of histones, which disrupts transcriptional control and induces cell cycle arrest and apoptosis in the parasite (nih.gov, googleapis.com). While several HDAC inhibitors are approved for cancer therapy, the development of parasitic HDAC inhibitors focuses on achieving high selectivity for the parasite's enzymes over human HDACs to minimize host toxicity (nih.gov, uni-halle.de). Consequently, parasitic HDACs represent a promising frontier for the development of new treatments for neglected tropical diseases and drug-resistant parasitic infections (nih.gov, ingentaconnect.com). The structural differences between parasitic and human HDAC isoforms, such as SmHDAC8, provide opportunities for the design of parasite-specific inhibitors (uni-halle.de). Research into these targets is driven by the need for new antiprotozoal agents that can overcome existing drug resistance (nih.gov).

Other names

Parasitic HDACProtozoal histone deacetylaseHelminth histone deacetylaseHistone deacetylase (parasitic)

Inhibition of the catalytic activity of histone deacetylases, leading to hyperacetylation of histones and non-histone proteins, which causes transcriptional dysregulation, cell cycle arrest, and apoptosis in the parasite (nih.gov, googleapis.com).