ArticleThe Journal of clinical investigation2014
Prion disease tempo determined by host-dependent substrate reduction.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
49 citing papers in PubMed, 70 citations in OpenAlex.
- Rapidly progressive Alzheimer's disease features distinct structures of amyloid-β.Brain : a journal of neurology · 2015Trial
- PrP turnover in vivo and the time to effect of prion disease therapeutics.PLoS pathogens · 2026Article
- Prion-induced ferroptosis is facilitated by RAC3.Nature communications · 2025Article
- Structural exposure of different microtubule binding domains determines the propagation and toxicity of pathogenic tau conformers in Alzheimer's disease.PLoS pathogens · 2025Article
- Prion Protein Endoproteolysis: Cleavage Sites, Mechanisms and Connections to Prion Disease.Journal of neurochemistry · 2025Review
- The dynamics of prion spreading is governed by the interplay between the non-linearities of tissue response and replication kinetics.iScience · 2024Article
- Review
- Update on a brain-penetrant cardiac glycoside that can lower cellular prion protein levels in human and guinea pig paradigms.PloS one · 2024Article
- Prion assemblies: structural heterogeneity, mechanisms of formation, and role in species barrier.Cell and tissue research · 2023Review
- Mechanisms of prion-induced toxicity.Cell and tissue research · 2023Review
- Beta-endoproteolysis of the cellular prion protein by dipeptidyl peptidase-4 and fibroblast activation protein.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Prion protein with a mutant N-terminal octarepeat region undergoes cobalamin-dependent assembly into high-molecular weight complexes.The Journal of biological chemistry · 2022Article
- Distinct populations of highly potent TAU seed conformers in rapidly progressing Alzheimer's disease.Science translational medicine · 2022Article
- Endoproteolysis of cellular prion protein by plasmin hinders propagation of prions.Frontiers in molecular neuroscience · 2022Article
- Article
- Investigating CRISPR/Cas9 gene drive for production of disease-preventing prion gene alleles.PloS one · 2022Article
- Membrane Domain Localization and Interaction of the Prion-Family Proteins, Prion and Shadoo with Calnexin.Membranes · 2021Article
- Harnessing the Physiological Functions of Cellular Prion Protein in the Kidneys: Applications for Treating Renal Diseases.Biomolecules · 2021Review
- Quaternary Structure Changes for PrPMolecular neurobiology · 2021Article
- Incomplete glycosylation during prion infection unmasks a prion protein epitope that facilitates prion detection and strain discrimination.The Journal of biological chemistry · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 6 institutions in 5 countries.
Funding
Abstract
The symptoms of prion infection can take years or decades to manifest following the initial exposure. Molecular markers of prion disease include accumulation of the misfolded prion protein (PrPSc), which is derived from its cellular precursor (PrPC), as well as downregulation of the PrP-like Shadoo (Sho) glycoprotein. Given the overlapping cellular environments for PrPC and Sho, we inferred that PrPC levels might also be altered as part of a host response during prion infection. Using rodent models, we found that, in addition to changes in PrPC glycosylation and proteolytic processing, net reductions in PrPC occur in a wide range of prion diseases, including sheep scrapie, human Creutzfeldt-Jakob disease, and cervid chronic wasting disease. The reduction in PrPC results in decreased prion replication, as measured by the protein misfolding cyclic amplification technique for generating PrPSc in vitro. While PrPC downregulation is not discernible in animals with unusually short incubation periods and high PrPC expression, slowly evolving prion infections exhibit downregulation of the PrPC substrate required for new PrPSc synthesis and as a receptor for pathogenic signaling. Our data reveal PrPC downregulation as a previously unappreciated element of disease pathogenesis that defines the extensive, presymptomatic period for many prion strains.
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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.