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The Toll-Like Receptor Agonist Imiquimod Is Active against Prions

Using a yeast-based assay, a previously unsuspected antiprion activity was found for imiquimod (IQ), a potent Toll-like receptor 7 (TLR7) agonist already used for clinical applications. The antiprion activity of IQ was first detected against yeast prions [PSI (+)] and [URE3], and then against mammal...

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Autores principales: Oumata, Nassima, Nguyen, Phu hai, Beringue, Vincent, Soubigou, Flavie, Pang, Yanhong, Desban, Nathalie, Massacrier, Catherine, Morel, Yannis, Paturel, Carine, Contesse, Marie-Astrid, Bouaziz, Serge, Sanyal, Suparna, Galons, Hervé, Blondel, Marc, Voisset, Cécile
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3745460/
https://www.ncbi.nlm.nih.gov/pubmed/23977222
http://dx.doi.org/10.1371/journal.pone.0072112
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author Oumata, Nassima
Nguyen, Phu hai
Beringue, Vincent
Soubigou, Flavie
Pang, Yanhong
Desban, Nathalie
Massacrier, Catherine
Morel, Yannis
Paturel, Carine
Contesse, Marie-Astrid
Bouaziz, Serge
Sanyal, Suparna
Galons, Hervé
Blondel, Marc
Voisset, Cécile
author_facet Oumata, Nassima
Nguyen, Phu hai
Beringue, Vincent
Soubigou, Flavie
Pang, Yanhong
Desban, Nathalie
Massacrier, Catherine
Morel, Yannis
Paturel, Carine
Contesse, Marie-Astrid
Bouaziz, Serge
Sanyal, Suparna
Galons, Hervé
Blondel, Marc
Voisset, Cécile
author_sort Oumata, Nassima
collection PubMed
description Using a yeast-based assay, a previously unsuspected antiprion activity was found for imiquimod (IQ), a potent Toll-like receptor 7 (TLR7) agonist already used for clinical applications. The antiprion activity of IQ was first detected against yeast prions [PSI (+)] and [URE3], and then against mammalian prion both ex vivo in a cell-based assay and in vivo in a transgenic mouse model for prion diseases. In order to facilitate structure-activity relationship studies, we conducted a new synthetic pathway which provides a more efficient means of producing new IQ chemical derivatives, the activity of which was tested against both yeast and mammalian prions. The comparable antiprion activity of IQ and its chemical derivatives in the above life forms further emphasizes the conservation of prion controlling mechanisms throughout evolution. Interestingly, this study also demonstrated that the antiprion activity of IQ and IQ-derived compounds is independent from their ability to stimulate TLRs. Furthermore, we found that IQ and its active chemical derivatives inhibit the protein folding activity of the ribosome (PFAR) in vitro.
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spelling pubmed-37454602013-08-23 The Toll-Like Receptor Agonist Imiquimod Is Active against Prions Oumata, Nassima Nguyen, Phu hai Beringue, Vincent Soubigou, Flavie Pang, Yanhong Desban, Nathalie Massacrier, Catherine Morel, Yannis Paturel, Carine Contesse, Marie-Astrid Bouaziz, Serge Sanyal, Suparna Galons, Hervé Blondel, Marc Voisset, Cécile PLoS One Research Article Using a yeast-based assay, a previously unsuspected antiprion activity was found for imiquimod (IQ), a potent Toll-like receptor 7 (TLR7) agonist already used for clinical applications. The antiprion activity of IQ was first detected against yeast prions [PSI (+)] and [URE3], and then against mammalian prion both ex vivo in a cell-based assay and in vivo in a transgenic mouse model for prion diseases. In order to facilitate structure-activity relationship studies, we conducted a new synthetic pathway which provides a more efficient means of producing new IQ chemical derivatives, the activity of which was tested against both yeast and mammalian prions. The comparable antiprion activity of IQ and its chemical derivatives in the above life forms further emphasizes the conservation of prion controlling mechanisms throughout evolution. Interestingly, this study also demonstrated that the antiprion activity of IQ and IQ-derived compounds is independent from their ability to stimulate TLRs. Furthermore, we found that IQ and its active chemical derivatives inhibit the protein folding activity of the ribosome (PFAR) in vitro. Public Library of Science 2013-08-16 /pmc/articles/PMC3745460/ /pubmed/23977222 http://dx.doi.org/10.1371/journal.pone.0072112 Text en © 2013 Oumata et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Oumata, Nassima
Nguyen, Phu hai
Beringue, Vincent
Soubigou, Flavie
Pang, Yanhong
Desban, Nathalie
Massacrier, Catherine
Morel, Yannis
Paturel, Carine
Contesse, Marie-Astrid
Bouaziz, Serge
Sanyal, Suparna
Galons, Hervé
Blondel, Marc
Voisset, Cécile
The Toll-Like Receptor Agonist Imiquimod Is Active against Prions
title The Toll-Like Receptor Agonist Imiquimod Is Active against Prions
title_full The Toll-Like Receptor Agonist Imiquimod Is Active against Prions
title_fullStr The Toll-Like Receptor Agonist Imiquimod Is Active against Prions
title_full_unstemmed The Toll-Like Receptor Agonist Imiquimod Is Active against Prions
title_short The Toll-Like Receptor Agonist Imiquimod Is Active against Prions
title_sort toll-like receptor agonist imiquimod is active against prions
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3745460/
https://www.ncbi.nlm.nih.gov/pubmed/23977222
http://dx.doi.org/10.1371/journal.pone.0072112
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