ArticleJournal of the American Chemical Society2018
Direct Observation of Murine Prion Protein Replication in Vitro.
Article in Journal of the American Chemical Society, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Probing the Energy Landscape of α-Synuclein Amyloid Fibril Formation by Systematic K-to-Q Mutagenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Leveraging the dominant-negative effect of the kuru-protective G127V prion protein variant as a novel therapeutic strategy.Neurobiology of disease · 2026Article
- Rapid elongation drives the exceptionally fast aggregation of the most common localized human amyloid medin.Communications chemistry · 2026Article
- Leveraging the dominant-negative effect of the kuru-protective G127V prion protein variant as a novel therapeutic strategy.bioRxiv : the preprint server for biology · 2026Article
- How does protein aggregate structure affect mechanisms of disaggregation?Biochemical Society transactions · 2025Review
- Direct Observation of Competing Prion Protein Fibril Populations with Distinct Structures and Kinetics.ACS nano · 2023Article
- Prion strains: shining new light on old concepts.Cell and tissue research · 2023Review
- Uncovering the universality of self-replication in protein aggregation and its link to disease.Science advances · 2022Article
- Molecular mechanisms of amyloid formation in living systems.Chemical science · 2022Review
- Hyperphosphorylated tau self-assembles into amorphous aggregates eliciting TLR4-dependent responses.Nature communications · 2022Article
- In vivo rate-determining steps of tau seed accumulation in Alzheimer's disease.Science advances · 2021Article
- Alpha Synuclein only Forms Fibrils In Vitro when Larger than its Critical Size of 70 Monomers.Chembiochem : a European journal of chemical biology · 2021Article
- Asymmetric-flow field-flow fractionation of prions reveals a strain-specific continuum of quaternary structures with protease resistance developing at a hydrodynamic radius of 15 nm.PLoS pathogens · 2021Article
- Super-resolution imaging reveals α-synuclein seeded aggregation in SH-SY5Y cells.Communications biology · 2021Article
- Scaling analysis reveals the mechanism and rates of prion replication in vivo.Nature structural & molecular biology · 2021Article
- Single Molecule Characterization of Amyloid Oligomers.Molecules (Basel, Switzerland) · 2021Review
- High-Speed Atomic Force Microscopy Reveals the Structural Dynamics of the Amyloid-β and Amylin Aggregation Pathways.International journal of molecular sciences · 2020Review
- α-Synuclein strains target distinct brain regions and cell types.Nature neuroscience · 2020Article
- Imaging individual protein aggregates to follow aggregation and determine the role of aggregates in neurodegenerative disease.Biochimica et biophysica acta. Proteins and proteomics · 2019Review
- Prion protein-Semisynthetic prion protein (PrP) variants with posttranslational modifications.Journal of peptide science : an official publication of the European Peptide Society · 2019Review
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Authors and funding
8 authors.
Funding
Abstract
Prions are believed to propagate when an assembly of prion protein (PrP) enters a cell and replicates to produce two or more fibrils, leading to an exponential increase in PrP aggregate number with time. However, the molecular basis of this process has not yet been established in detail. Here, we use single-aggregate imaging to study fibril fragmentation and elongation of individual murine PrP aggregates from seeded aggregation in vitro. We found that PrP elongation occurs via a structural conversion from a PK-sensitive to PK-resistant conformer. Fibril fragmentation was found to be length-dependent and resulted in the formation of PK-sensitive fragments. Measurement of the rate constants for these processes also allowed us to predict a simple spreading model for aggregate propagation through the brain, assuming that doubling of the aggregate number is rate-limiting. In contrast, while α-synuclein aggregated by the same mechanism, it showed significantly slower elongation and fragmentation rate constants than PrP, leading to much slower replication rate. Overall, our study shows that fibril elongation with fragmentation are key molecular processes in PrP and α-synuclein aggregate replication, an important concept in prion biology, and also establishes a simple framework to start to determine the main factors that control the rate of prion and prion-like spreading in animals.
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Registered trials
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