ArticleProceedings of the National Academy of Sciences of the United States of America2013
Unique drug screening approach for prion diseases identifies tacrolimus and astemizole as antiprion agents.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 94 citations in OpenAlex.
- Phenotypic screening for small molecules that lower PrP in cultured cells.Molecular and cellular neurosciences · 2026Article
- Prion Diseases-When Proteins Turn Lethal: Creutzfeldt-Jakob Disease (CJD) and the Quest for Classification, Diagnosis, Therapeutic Approaches, and Emerging Research.Molecules (Basel, Switzerland) · 2026Review
- Phenotypic screening for small molecules that lower PrP in cultured cells.bioRxiv : the preprint server for biology · 2026Article
- One organelle to rule them all: enhancement of lysosomal activity as a therapeutic modality for protein misfolding neurodegenerative diseases.Frontiers in neuroscience · 2026Review
- Contrasting roles of autophagy in cellular prion infection.Autophagy · 2025Article
- Optical biosensors for diagnosing neurodegenerative diseases.Npj biosensing · 2025Review
- Adaptation of the protein misfolding cyclic amplification (PMCA) technique for the screening of anti-prion compounds.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Astemizole, a Second-Generation Histamine H1-Receptor Antagonist, Did Not Attenuate the Aggregation Process of α-Synuclein In Vitro.Biomedicines · 2024Article
- Melatonin inhibits Japanese encephalitis virus replication and neurotoxicity via calcineurin-autophagy pathways.BMC neuroscience · 2023Article
- Therapeutic strategies for identifying small molecules against prion diseases.Cell and tissue research · 2023Review
- Identification of a Cardiac Glycoside Exhibiting Favorable Brain Bioavailability and Potency for Reducing Levels of the Cellular Prion Protein.International journal of molecular sciences · 2022Article
- Article
- Proteostasis unbalance in prion diseases: Mechanisms of neurodegeneration and therapeutic targets.Frontiers in neuroscience · 2022Review
- Novel regulators of PrPC biosynthesis revealed by genome-wide RNA interference.PLoS pathogens · 2021Article
- 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
- Cross-Linking Cellular Prion Protein Induces Neuronal Type 2-Like Hypersensitivity.Frontiers in immunology · 2021Article
- An Ex Vivo Brain Slice Culture Model of Chronic Wasting Disease: Implications for Disease Pathogenesis and Therapeutic Development.Scientific reports · 2020Article
- An Update on Autophagy in Prion Diseases.Frontiers in bioengineering and biotechnology · 2020Review
- Identifying Anti-prion Chemical Compounds Using a Newly Established Yeast High-Throughput Screening System.Cell chemical biology · 2019Article
- Autophagy pathways in the treatment of prion diseases.Current opinion in pharmacology · 2019Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Prion diseases such as Creutzfeldt-Jakob disease (CJD) are incurable and rapidly fatal neurodegenerative diseases. Because prion protein (PrP) is necessary for prion replication but dispensable for the host, we developed the PrP-FRET-enabled high throughput assay (PrP-FEHTA) to screen for compounds that decrease PrP expression. We screened a collection of drugs approved for human use and identified astemizole and tacrolimus, which reduced cell-surface PrP and inhibited prion replication in neuroblastoma cells. Tacrolimus reduced total cellular PrP levels by a nontranscriptional mechanism. Astemizole stimulated autophagy, a hitherto unreported mode of action for this pharmacophore. Astemizole, but not tacrolimus, prolonged the survival time of prion-infected mice. Astemizole is used in humans to treat seasonal allergic rhinitis in a chronic setting. Given the absence of any treatment option for CJD patients and the favorable drug characteristics of astemizole, including its ability to cross the blood-brain barrier, it may be considered as therapy for CJD patients and for prophylactic use in familial prion diseases. Importantly, our results validate PrP-FEHTA as a method to identify antiprion compounds and, more generally, FEHTA as a unique drug discovery platform.
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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.