The Toll-like Receptor Agonist Imiquimod is Active Against Prions

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Aug 27

PMID 23977222

Citations 13

Authors

Nassima Oumata

Phu Hai Nguyen

Vincent Beringue

Flavie Soubigou

Yanhong Pang

Nathalie Desban

Catherine Massacrier

Yannis Morel

Carine Paturel

Marie-Astrid Contesse

Serge Bouaziz

Suparna Sanyal

Herve Galons

Marc Blondel

Cecile Voisset

Affiliations

Soon will be listed here.

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.

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