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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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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. |
format | Online Article Text |
id | pubmed-3745460 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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