ArticleProceedings of the National Academy of Sciences of the United States of America2014
Quinacrine promotes replication and conformational mutation of chronic wasting disease prions.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 61 citations in OpenAlex.
- A scalable, dividing cell model for the robust propagation and quantification of human sporadic Creutzfeldt-Jakob disease prions.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Distinct prion conformers from brain and peripheral tissues of gene-targeted mice produce convergent CWD strain properties.PLoS pathogens · 2026Article
- Regulated coexpression of PrP from different species in mice impacts the replication and host range properties of prion strains.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- Reactive Microglia and Astrocytes as Therapeutic Targets in Prion Diseases.Sub-cellular biochemistry · 2025Review
- Propagation of distinct CWD prion strains during peripheral and intracerebral challenges of gene-targeted mice.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Sodium hypochlorite inactivation of human CJD prions.PloS one · 2024Article
- Disease phenotype of classical sheep scrapie is changed upon experimental passage through white-tailed deer.PLoS pathogens · 2023Article
- Vaccines for prion diseases: a realistic goal?Cell and tissue research · 2023Review
- A single protective polymorphism in the prion protein blocks cross-species prion replication in cultured cells.Journal of neurochemistry · 2023Article
- New developments in prion disease research using genetically modified mouse models.Cell and tissue research · 2023Review
- Article
- Adipose-derived mesenchymal stromal cells decrease prion-induced glial inflammation in vitro.Scientific reports · 2022Article
- Review
- Alternating anti-prion regimens reduce combination drug resistance but do not further extend survival in scrapie-infected mice.The Journal of general virology · 2021Article
- Article
- Cervid Prion Protein Polymorphisms: Role in Chronic Wasting Disease Pathogenesis.International journal of molecular sciences · 2021Review
- Incomplete glycosylation during prion infection unmasks a prion protein epitope that facilitates prion detection and strain discrimination.The Journal of biological chemistry · 2020Article
- An Ex Vivo Brain Slice Culture Model of Chronic Wasting Disease: Implications for Disease Pathogenesis and Therapeutic Development.Scientific reports · 2020Article
- Emergence of prions selectively resistant to combination drug therapy.PLoS pathogens · 2020Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Quinacrine's ability to reduce levels of pathogenic prion protein (PrP(Sc)) in mouse cells infected with experimentally adapted prions led to several unsuccessful clinical studies in patients with prion diseases, a 10-y investment to understand its mechanism of action, and the production of related compounds with expectations of greater efficacy. We show here, in stark contrast to this reported inhibitory effect, that quinacrine enhances deer and elk PrP(Sc) accumulation and promotes propagation of prions causing chronic wasting disease (CWD), a fatal, transmissible, neurodegenerative disorder of cervids of uncertain zoonotic potential. Surprisingly, despite increased prion titers in quinacrine-treated cells, transmission of the resulting prions produced prolonged incubation times and altered PrP(Sc) deposition patterns in the brains of diseased transgenic mice. This unexpected outcome is consistent with quinacrine affecting the intrinsic properties of the CWD prion. Accordingly, quinacrine-treated CWD prions were comprised of an altered PrP(Sc) conformation. Our findings provide convincing evidence for drug-induced conformational mutation of prions without the prerequisite of generating drug-resistant variants of the original strain. More specifically, they show that a drug capable of restraining prions in one species/strain setting, and consequently used to treat human prion diseases, improves replicative ability in another and therefore force reconsideration of current strategies to screen antiprion compounds.
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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.