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The Toll-Like Receptor Agonist Imiquimod Is Active against Prions
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2013 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 8, no 8, e72112- p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2013. Vol. 8, no 8, e72112- p.
National Category
Medical and Health Sciences Natural Sciences
URN: urn:nbn:se:uu:diva-208085DOI: 10.1371/journal.pone.0072112ISI: 000323570200059OAI: oai:DiVA.org:uu-208085DiVA: diva2:650827
Available from: 2013-09-23 Created: 2013-09-23 Last updated: 2013-09-23Bibliographically approved

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Pang, YanhongSanyal, Suparna
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