ArticlePloS one2008
Antihypertensive drug guanabenz is active in vivo against both yeast and mammalian prions.
Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 107 citations in OpenAlex.
- Protein misfolding, amyotrophic lateral sclerosis and guanabenz: protocol for a phase II RCT with futility design (ProMISe trial).BMJ open · 2017Trial
- Pediatric pharmacokinetics and pharmacodynamics of guanabenz for the treatment of vanishing white matter.Scientific reports · 2026Article
- The Construction of ceRNA Regulatory Network Unraveled Prognostic Biomarkers and Repositioned Drug Candidates for the Management of Pancreatic Ductal Adenocarcinoma.Current issues in molecular biology · 2025Article
- Exploring immunotherapeutic strategies for neurodegenerative diseases: a focus on Huntington's disease and Prion diseases.Acta pharmacologica Sinica · 2025Review
- Potential of Marine Sponge Metabolites against Prions: Bromotyrosine Derivatives, a Family of Interest.Marine drugs · 2024Article
- Prion therapeutics: Lessons from the past.Prion · 2022Review
- Guanabenz ameliorates disease in vanishing white matter mice in contrast to sephin1.Annals of clinical and translational neurology · 2022Article
- Protein synthesis modulation as a therapeutic approach for amyotrophic lateral sclerosis and frontotemporal dementia.Neural regeneration research · 2022Review
- Pharmacological targeting of endoplasmic reticulum stress in disease.Nature reviews. Drug discovery · 2022Review
- Chemical Chaperones to Inhibit Endoplasmic Reticulum Stress: Implications in Diseases.Drug design, development and therapy · 2022Review
- The Unfolded Protein Responses in Health, Aging, and Neurodegeneration: Recent Advances and Future Considerations.Frontiers in molecular neuroscience · 2022Review
- Anti-prion Drugs Targeting the Protein Folding Activity of the Ribosome Reduce PABPN1 Aggregation.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- Review
- Ribosomal RNA Modulates Aggregation of theInternational journal of molecular sciences · 2020Article
- Sephin1 Reduces Prion Infection in Prion-Infected Cells and Animal Model.Molecular neurobiology · 2020Article
- Identifying Anti-prion Chemical Compounds Using a Newly Established Yeast High-Throughput Screening System.Cell chemical biology · 2019Article
- The antibiotic robenidine exhibits guanabenz-like cytoprotective properties by a mechanism independent of protein phosphatase PP1:PPP1R15A.The Journal of biological chemistry · 2019Article
- Review
- Autophagy stimulation as a promising approach in treatment of neurodegenerative diseases.Metabolic brain disease · 2018Review
- Guanabenz promotes neuronal survival via enhancement of ATF4 and parkin expression in models of Parkinson disease.Experimental neurology · 2018Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPrion-based diseases are incurable transmissible neurodegenerative disorders affecting animals and humans. METHODOLOGY/PRINCIPAL
findingsHere we report the discovery of the in vivo antiprion activity of Guanabenz (GA), an agonist of alpha2-adrenergic receptors routinely used in human medicine as an antihypertensive drug. We isolated GA in a screen for drugs active in vivo against two different yeast prions using a previously described yeast-based two steps assay. GA was then shown to promote ovine PrP(Sc) clearance in a cell-based assay. These effects are very specific as evidenced by the lack of activity of some GA analogues that we generated. GA antiprion activity does not involve its agonist activity on alpha2-adrenergic receptors as other chemically close anti-hypertensive agents possessing related mechanism of action were found inactive against prions. Finally, GA showed activity in a transgenic mouse-based in vivo assay for ovine prion propagation, prolonging slightly but significantly the survival of treated animals. CONCLUSION/SIGNIFICANCE: GA thus adds to the short list of compounds active in vivo in animal models for the treatment of prion-based diseases. Because it has been administrated for many years to treat hypertension on a daily basis, without major side-effects, our results suggest that it could be evaluated in human as a potential treatment for prion-based diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.