ArticlePloS one2010
A new method for the characterization of strain-specific conformational stability of protease-sensitive and protease-resistant PrPSc.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
37 citing papers in PubMed.
- Rapidly progressive Alzheimer's disease features distinct structures of amyloid-β.Brain : a journal of neurology · 2015Trial
- D178N prion protein mutation endows RML prions with new strain properties that do not mimic human genetic prion diseases.Acta neuropathologica · 2026Article
- Substitution of histidine 95 by tyrosine in the prion protein causes spontaneous neurodegeneration in transgenic mice.PLoS pathogens · 2025Article
- Efficient transmission of human prion diseases to a glycan-free prion protein-expressing host.Brain : a journal of neurology · 2024Article
- Prion strains: shining new light on old concepts.Cell and tissue research · 2023Review
- A single amino acid residue in bank vole prion protein drives permissiveness to Nor98/atypical scrapie and the emergence of multiple strain variants.PLoS pathogens · 2022Article
- Chronic wasting disease (CWD) prion strains evolve via adaptive diversification of conformers in hosts expressing prion protein polymorphisms.The Journal of biological chemistry · 2020Article
- Formation of distinct prion protein amyloid fibrils under identical experimental conditions.Scientific reports · 2020Article
- Novel Strain of the Chronic Wasting Disease Agent Isolated From Experimentally Inoculated Elk With LL132 Prion Protein.Scientific reports · 2020Article
- Understanding Prion Strains: Evidence from Studies of the Disease Forms Affecting Humans.Viruses · 2019Review
- Recent advances in the histo-molecular pathology of human prion disease.Brain pathology (Zurich, Switzerland) · 2019Review
- Co-occurrence of chronic traumatic encephalopathy and prion disease.Acta neuropathologica communications · 2018Article
- Pathologic and biochemical characterization of PrPBMC veterinary research · 2018Article
- Source genotype influence on cross species transmission of transmissible spongiform encephalopathies evaluated by RT-QuIC.PloS one · 2018Article
- Article
- Self-propagating, protease-resistant, recombinant prion protein conformers with or without in vivo pathogenicity.PLoS pathogens · 2017Article
- Prion Strain Characterization of a Novel Subtype of Creutzfeldt-Jakob Disease.Journal of virology · 2017Article
- Novel strain properties distinguishing sporadic prion diseases sharing prion protein genotype and prion type.Scientific reports · 2017Article
- PrPC Governs Susceptibility to Prion Strains in Bank Vole, While Other Host Factors Modulate Strain Features.Journal of virology · 2016Article
- Isolation of a Defective Prion Mutant from Natural Scrapie.PLoS pathogens · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although proteinacious in nature, prions exist as strains with specific self-perpetuating biological properties. Prion strains are thought to be associated with different conformers of PrP(Sc), a disease-associated isoform of the host-encoded cellular protein (PrP(C)). Molecular strain typing approaches have been developed which rely on the characterization of protease-resistant PrP(Sc). However, PrP(Sc) is composed not only of protease-resistant but also of protease-sensitive isoforms. The aim of this work was to develop a protocol for the molecular characterization of both, protease-resistant and protease-sensitive PrP(Sc) aggregates. We first set up experimental conditions which allowed the most advantageous separation of PrP(C) and PrP(Sc) by means of differential centrifugation. The conformational solubility and stability assay (CSSA) was then developed by measuring PrP(Sc) solubility as a function of increased exposure to GdnHCl. Brain homogenates from voles infected with human and sheep prion isolates were analysed by CSSA and showed strain-specific conformational stabilities, with mean [GdnHCl](1/2) values ranging from 1.6 M for MM2 sCJD to 2.1 for scrapie and to 2.8 M for MM1/MV1 sCJD and E200K gCJD. Interestingly, the rank order of [GdnHCl](1/2) values observed in the human and sheep isolates used as inocula closely matched those found following transmission in voles, being MM1 sCJD the most resistant (3.3 M), followed by sheep scrapie (2.2 M) and by MM2 sCJD (1.6 M). In order to test the ability of CSSA to characterise protease-sensitive PrP(Sc), we analysed sheep isolates of Nor98 and compared them to classical scrapie isolates. In Nor98, insoluble PrP(Sc) aggregates were mainly protease-sensitive and showed a conformational stability much lower than in classical scrapie. Our results show that CSSA is able to reveal strain-specified PrP(Sc) conformational stabilities of protease-resistant and protease-sensitive PrP(Sc) and that it is a valuable tool for strain typing in natural hosts, such as humans and sheep.
Indexed as
Identifiers
What OpenQuestion holds
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.