ArticleNature2011
Prion propagation and toxicity in vivo occur in two distinct mechanistic phases.
Article in Nature, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 192 papers.
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Who cites it
192 citing papers in PubMed, 309 citations in OpenAlex.
- Disease Progression in Iatrogenic Cerebral Amyloid Angiopathy.Neurology · 2026Article
- Article
- Successful bioassay of blood from chronic wasting disease-affected cervids in cervid PrP transgenic Drosophila.Acta neuropathologica communications · 2026Article
- 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
- Prion propagation is controlled by discrete structural regions of PrP rather than overall stability.The Journal of biological chemistry · 2026Article
- Enhanced lysosomal activity prevents infection with PrPThe Journal of biological chemistry · 2026Article
- Presymptomatic pharmacological inhibition of mGluR5 improves survival in a mouse model of prion diseases.Acta neuropathologica communications · 2026Article
- Stereotaxic Delivery of M1000 Prions to the Hippocampus Induces Related Behavioural and Cognitive Changes Consistent with Acute Neurotoxic Effects.Molecular neurobiology · 2025Article
- Intracellular trafficking SNARE protein, syntaxin-6, modifies prion cellular phenotypes and risk of disease development in vivo.Acta neuropathologica · 2025Article
- Soluble N-terminal region of prion protein causes rapid neurodegeneration in prion disease.Science advances · 2025Article
- Yeast Prions: Discovery, Nature, Cellular Manipulation and Implication.Journal of microbiology and biotechnology · 2025Review
- Prion replication in organotypic brain slice cultures is distinct from in vivo inoculation and is species dependent.Acta neuropathologica communications · 2025Article
- Investigating the In Vivo Effects of Anti-Prion Protein Nanobodies on Prion Disease with AAV Vector.Pathogens (Basel, Switzerland) · 2025Article
- Human Genetic Evidence for New Targets in Prion Diseases: Opportunities and Challenges.Sub-cellular biochemistry · 2025Review
- Iatrogenic cerebral amyloid angiopathy: more cases to come.Frontiers in neurology · 2025Article
- Prion protein fragment (106-126) activates NLRP3 inflammasome and promotes platelet-monocyte/neutrophil interactions, potentially contributing to an inflammatory state.Frontiers in cell and developmental biology · 2025Article
- Single-cell transcriptomics unveils molecular signatures of neuronal vulnerability in a mouse model of prion disease that overlap with Alzheimer's disease.Nature communications · 2024Article
- Article
- Cleavage site-directed antibodies reveal the prion protein in humans is shed by ADAM10 at Y226 and associates with misfolded protein deposits in neurodegenerative diseases.Acta neuropathologica · 2024Article
- Efficient transmission of human prion diseases to a glycan-free prion protein-expressing host.Brain : a journal of neurology · 2024Article
132 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Mammalian prions cause fatal neurodegenerative conditions including Creutzfeldt-Jakob disease in humans and scrapie and bovine spongiform encephalopathy in animals. Prion infections are typically associated with remarkably prolonged but highly consistent incubation periods followed by a rapid clinical phase. The relationship between prion propagation, generation of neurotoxic species and clinical onset has remained obscure. Prion incubation periods in experimental animals are known to vary inversely with expression level of cellular prion protein. Here we demonstrate that prion propagation in brain proceeds via two distinct phases: a clinically silent exponential phase not rate-limited by prion protein concentration which rapidly reaches a maximal prion titre, followed by a distinct switch to a plateau phase. The latter determines time to clinical onset in a manner inversely proportional to prion protein concentration. These findings demonstrate an uncoupling of infectivity and toxicity. We suggest that prions themselves are not neurotoxic but catalyse the formation of such species from PrP(C). Production of neurotoxic species is triggered when prion propagation saturates, leading to a switch from autocatalytic production of infectivity (phase 1) to a toxic (phase 2) pathway.
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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.