Portal de Periódicos da CAPES

Artigo Produção Nacional Revisado por pares

BIBTEX RIS

Deubiquitinating enzymes as possible drug targets for schistosomiasis

2021; Elsevier BV; Volume: 217; Linguagem: Inglês

10.1016/j.actatropica.2021.105856

1873-6254

Andressa Barban do Patrocínio, Fernanda Janku Cabral, Thales Henrique de Paiva, Lizandra Guidi Magalhães, Lucas Antônio de Lima Paula, Olinda Mara Brigato, Renata Guerra‐Sá, Vanderlei Rodrigues,

Research on Leishmaniasis Studies

Deubiquitinating enzymes (DUBs) are conserved in Schistosoma mansoni and may be linked to the 26S proteasome. Previous results from our group showed that b-AP15, an inhibitor of the 26S proteasome DUBs UCHL5 and USP14 induced structural and gene expression changes in mature S. mansoni pairs. This work suggests the use of the nonselective DUB inhibitor PR-619 to verify whether these enzymes are potential target proteins for new drug development. Our approach is based on previous studies with DUB inhibitors in mammalian cells that have shown that these enzymes are associated with apoptosis, autophagy and the transforming growth factor beta (TGF-β) signaling pathway. PR-619 inhibited oviposition in parasite pairs in vitro, leading to mitochondrial changes, autophagic body formation, and changes in expression of SmSmad2 and SmUSP9x, which are genes linked to the TGF-β pathway that are responsible for parasite oviposition and SmUCHL5 and SmRpn11 DUB maintenance. Taken together, these results indicate that DUBs may be used as targets for the development of new drugs against schistosomiasis.