Research article2013Peer reviewedOpen access
The Toll-Like Receptor Agonist Imiquimod Is Active against Prions
Oumata, Nassima; Phu Hai Nguyen; Beringue, Vincent; Soubigou, Flavie; Pang, Yanhong; Desban, Nathalie; Massacrier, Catherine; Morel, Yannis; Paturel, Carine; Contesse, Marie-Astrid; Bouaziz, Serge; Sanyal, Suparna; Galons, Herve; Blondel, Marc; Voisset, Cecile
Abstract
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.
Published in
PLoS ONE
2013, Volume: 8, number: 8, article number: e72112
UKÄ Subject classification
Biochemistry and Molecular Biology
Cell Biology
Publication identifier
DOI: https://doi.org/10.1371/journal.pone.0072112
Permanent link to this page (URI)
https://res.slu.se/id/publ/87069