Related Experiment Video
Updated: May 8, 2026
Real-time Quaking-induced Conversion Assay for Detection of CWD Prions in Fecal Material
Published on: September 29, 2017
The toll-like receptor agonist imiquimod is active against prions
Nassima Oumata1, Phu Hai Nguyen, Vincent Beringue
1Laboratoire de Chimie Organique 2, INSERM U1022, Université Paris Descartes, Paris, France.
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.
Insights
Imiquimod (IQ), a clinical drug, unexpectedly shows antiprion activity against yeast and mammalian prions. This activity, independent of Toll-like receptor 7 (TLR7) stimulation, involves inhibiting the ribosome's protein folding activity.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Prion diseases are fatal neurodegenerative disorders caused by misfolded proteins.
- Imiquimod (IQ) is an established Toll-like receptor 7 (TLR7) agonist with clinical applications.
- Yeast prions serve as model systems for studying prion propagation and inhibition.
Purpose of the Study:
- To investigate the antiprion activity of imiquimod (IQ) and its derivatives.
- To explore the mechanism of IQ's antiprion effects.
- To assess the conservation of prion control mechanisms across species.
Main Methods:
- Yeast-based assays were used to screen for antiprion activity against yeast prions [PSI (+)] and [URE3].
- Cell-based assays and a transgenic mouse model were employed to evaluate IQ's efficacy against mammalian prions.
- A novel synthetic pathway was developed for generating IQ derivatives to study structure-activity relationships.
- In vitro assays were conducted to determine the effect of IQ and derivatives on ribosome protein folding activity (PFAR).
Main Results:
- Imiquimod (IQ) demonstrated significant antiprion activity against both yeast and mammalian prions.
- IQ derivatives, synthesized via a new pathway, exhibited comparable antiprion efficacy.
- The antiprion activity of IQ and its derivatives was found to be independent of TLR7 stimulation.
- IQ and its active derivatives were shown to inhibit the protein folding activity of the ribosome (PFAR) in vitro.
Conclusions:
- Imiquimod (IQ) possesses a previously unrecognized antiprion activity with potential therapeutic implications.
- The conserved mechanisms of prion control across yeast and mammals highlight evolutionary links.
- IQ's antiprion mechanism involves the inhibition of ribosome protein folding activity (PFAR), distinct from its TLR7 agonism.
Related Concept Videos
01:29Immune Response Against Viral Pathogens
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
01:30Inhibitors of Viral Protein Synthesis
01:29Subviral Agents
01:27Tumor Immunotherapy