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Título: | Deubiquitinating enzymes as possible drug targets for schistosomiasis. |
Autor(es): | Patrocínio, Andressa Barban do Cabral, Fernanda Janku Paiva, Thales Henrique de Magalhães, Lizandra Guidi Paula, Lucas Antônio de Lima Brigato, Olinda Mara Cota, Renata Guerra de Sá Rodrigues, Vanderlei |
Palavras-chave: | PR-619 inhibitor Schistosoma mansoni |
Data do documento: | 2021 |
Referência: | PATROCÍNIO, A. B. do et al. Deubiquitinating enzymes as possible drug targets for schistosomiasis. Acta Tropica, v. 217, p. 105856, 2021. Disponível em: https://www.sciencedirect.com/science/article/abs/pii/S0001706X21000358?dgcid=rss_sd_all>. Acesso em: 10 jun. 2021. |
Resumo: | 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. |
URI: | http://www.repositorio.ufop.br/jspui/handle/123456789/14017 |
Link para o artigo: | https://www.sciencedirect.com/science/article/abs/pii/S0001706X21000358?dgcid=rss_sd_all |
DOI: | https://doi.org/10.1016/j.actatropica.2021.105856 |
ISSN: | 0001-706X |
Aparece nas coleções: | DECBI - Artigos publicados em periódicos |
Arquivos associados a este item:
Arquivo | Descrição | Tamanho | Formato | |
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ARTIGO_DeubiquitinatingEnzymesPossible.pdf Restricted Access | 8,46 MB | Adobe PDF | Visualizar/Abrir |
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