Schistosoma mansoni histone deacetylase 8 (SmHDAC8)

Schistosoma mansoni histone deacetylase 8 (SmHDAC8) is a class I zinc-dependent enzyme that plays a pivotal role in the epigenetic landscape of the trematode parasite responsible for schistosomiasis (Oger et al., 2010, PubMed: 20811465). It is expressed throughout all life stages of the parasite, including the infective cercariae and the adult worms residing in the human vasculature (Marek et al., 2013, PubMed: 23746552). SmHDAC8 functions by removing acetyl groups from lysine residues on histone tails and non-histone proteins, thereby modulating chromatin structure and gene expression essential for parasite survival and development (Heimburg et al., 2016, PubMed: 27380253). Due to its distinct structural differences from human HDAC8, particularly in the active site pocket, SmHDAC8 has emerged as a validated therapeutic target for the development of selective inhibitors (Schiedel et al., 2015, PubMed: 25664903). Inhibition of this enzyme results in significant mortality of schistosomula and adult worms, as well as a reduction in egg laying, which is the primary cause of pathology in the host (Tavares et al., 2022, PubMed: 35143542). Consequently, SmHDAC8 inhibitors represent a promising strategy for treating chronic schistosomiasis and overcoming potential resistance to praziquantel.

Other names

SmHDAC8Histone deacetylase 8Class I histone deacetylase 8

Inhibition of the zinc-dependent catalytic site of SmHDAC8, preventing the removal of acetyl groups from lysine residues on histones and non-histone proteins, which disrupts gene transcription and leads to parasite apoptosis and death (Marek et al., 2013, PubMed: 23746552; Heimburg et al., 2016, PubMed: 27380253).