ArticleJournal of virology2003
New inhibitors of scrapie-associated prion protein formation in a library of 2000 drugs and natural products.
Article in Journal of virology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
97 citing papers in PubMed, 232 citations in OpenAlex.
- Life at the interface: Byron Caughey's search for prion disease inhibitors through chemistry, structure, and cell physiology.Acta neuropathologica · 2026Review
- Prions and protein aggregates as pathogens, self-propagating structures, biomarkers, and therapeutic targets.Microbiology and molecular biology reviews : MMBR · 2025Review
- Screening of Anti-Prion Compounds Using the Protein Misfolding Cyclic Amplification Technology.Biomolecules · 2024Article
- 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
- Branched-Chain Amino Acid Assembly into Amyloid-like Fibrils Provides a New Paradigm for Maple Syrup Urine Disease Pathology.International journal of molecular sciences · 2023Article
- Pathways to healing: Plants with therapeutic potential for neurodegenerative diseases.IBRO neuroscience reports · 2023Article
- Recombinant ovine prion protein can be mutated at position 136 to improve its efficacy as an inhibitor of prion propagation.Scientific reports · 2023Article
- The Effect ofInternational journal of molecular sciences · 2022Article
- The protein aggregation inhibitor YAT2150 has potent antimalarial activity in Plasmodium falciparum in vitro cultures.BMC biology · 2022Article
- Structure-based discovery of small molecules that disaggregate Alzheimer's disease tissue derived tau fibrils in vitro.Nature communications · 2022Article
- Natural products for infectious microbes and diseases: an overview of sources, compounds, and chemical diversities.Science China. Life sciences · 2022Review
- Pentosan polysulfate induces low-level persistent prion infection keeping measurable seeding activity without PrP-res detection in Fukuoka-1 infected cell cultures.Scientific reports · 2022Article
- Carnosic Acid and Carnosol Display Antioxidant and Anti-Prion Properties in In Vitro and Cell-Free Models of Prion Diseases.Antioxidants (Basel, Switzerland) · 2022Article
- Hampering the early aggregation of PrP-E200K protein by charge-based inhibitors: a computational study.Journal of computer-aided molecular design · 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
- Green Tea Polyphenol Epigallocatechin-Gallate in Amyloid Aggregation and Neurodegenerative Diseases.Frontiers in neuroscience · 2021Review
- Multimodal small-molecule screening for human prion protein binders.The Journal of biological chemistry · 2020Article
- BMD42-2910, a Novel Benzoxazole Derivative, Shows a Potent Anti-prion Activity and Prolongs the Mean Survival in an Animal Model of Prion Disease.Experimental neurobiology · 2020Article
- Characterization of the Prion Protein Binding Properties of Antisense Oligonucleotides.Biomolecules · 2019Article
37 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Transmissible spongiform encephalopathies (TSEs) are fatal, untreatable neurodegenerative diseases associated with the accumulation of a disease-specific form of prion protein (PrP) in the brain. One approach to TSE therapeutics is the inhibition of PrP accumulation. Indeed, many inhibitors of the accumulation of PrP associated with scrapie (PrP(Sc)) in scrapie-infected mouse neuroblastoma cells (ScN(2)a) also have antiscrapie activity in rodents. To expedite the search for potential TSE therapeutic agents, we have developed a high-throughput screening assay for PrP(Sc) inhibitors using ScN(2)a cells in a 96-well format. A library of 2000 drugs and natural products was screened in ScN(2)a cells infected with scrapie strain RML (Chandler) or 22L. Forty compounds were found to have concentrations causing 50% inhibition (IC(50)s) of PrP(Sc) accumulation of <or=10 microM against both strains. Seventeen had IC(50)s of <or=1 microM against both strains. Several classes of compounds were represented in the 17 most potent inhibitors, including naturally occurring polyphenols (e.g., tannic acid and tea extracts), phenothiazines, antihistamines, statins, and antimalarial compounds. These 17 compounds were also evaluated in a solid-phase cell-free hamster PrP conversion assay. Only the polyphenols inhibited the cell-free reaction, and their IC(50)s were near 100 nM. Several of the new PrP(Sc) inhibitors cross the blood-brain barrier and thus have potential to be effective after TSE infection reaches the brain. The fact that many are either approved human drugs or edible natural products should facilitate their use in animal testing and clinical trials.
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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.