ArticleThe EMBO journal2011
The cellular prion protein mediates neurotoxic signalling of β-sheet-rich conformers independent of prion replication.
Article in The EMBO journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 148 papers.
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Who cites it
148 citing papers in PubMed, 241 citations in OpenAlex.
- Bovine Spongiform Encephalopathy: An Integrated Review of Prion Mechanisms, Neuroanatomy, and Control.Veterinary sciences · 2026Review
- Presymptomatic pharmacological inhibition of mGluR5 improves survival in a mouse model of prion diseases.Acta neuropathologica communications · 2026Article
- Time-dependent transcriptomic response to scrapie exposure in ovine MSC-derived neuron-like cells.Frontiers in cellular and infection microbiology · 2026Article
- Cellular prion protein and calcium ions trigger the neurotoxicity of α-synuclein aggregates.Cell & bioscience · 2025Article
- Pathological and Functional Brain Amyloids: A New Concept Explaining the Differences.International journal of molecular sciences · 2025Review
- The structure of complexes between zinc(ii) cations and histidine-rich repeats from the unstructured N-terminal domain of human prion protein.RSC advances · 2025Review
- Topological confinement by a membrane anchor suppresses phase separation into protein aggregates: Implications for prion diseases.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Comparing Prion Proteins Across Species: Is Zebrafish a Useful Model?Molecular neurobiology · 2025Review
- Fyn Kinase in Alzheimer's Disease: Unraveling Molecular Mechanisms and Therapeutic Implications.Molecular neurobiology · 2025Review
- Efficient enzyme-free isolation of brain-derived extracellular vesicles.Journal of extracellular vesicles · 2024Article
- Prion protein pathology in Ubiquilin 2 models of ALS.Neurobiology of disease · 2024Article
- The cellular prion protein does not affect tau seeding and spreading of sarkosyl-insoluble fractions from Alzheimer's disease.Scientific reports · 2024Article
- α-Synuclein strain propagation is independent of cellular prion protein expression in a transgenic synucleinopathy mouse model.PLoS pathogens · 2024Article
- 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
- Polyphenol-based polymer nanoparticles for inhibiting amyloid protein aggregation: recent advances and perspectives.Frontiers in nutrition · 2024Review
- Amyloids and prions in the light of evolution.Current genetics · 2023Review
- Inducing prion protein shedding as a neuroprotective and regenerative approach in pathological conditions of the brain: from theory to facts.Neural regeneration research · 2023Review
- Anchorless risk or released benefit? An updated view on the ADAM10-mediated shedding of the prion protein.Cell and tissue research · 2023Review
- Rapid ex vivo reverse genetics identifies the essential determinants of prion protein toxicity.Brain pathology (Zurich, Switzerland) · 2023Article
- Review
88 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Formation of aberrant protein conformers is a common pathological denominator of different neurodegenerative disorders, such as Alzheimer's disease or prion diseases. Moreover, increasing evidence indicates that soluble oligomers are associated with early pathological alterations and that oligomeric assemblies of different disease-associated proteins may share common structural features. Previous studies revealed that toxic effects of the scrapie prion protein (PrP(Sc)), a β-sheet-rich isoform of the cellular PrP (PrP(C)), are dependent on neuronal expression of PrP(C). In this study, we demonstrate that PrP(C) has a more general effect in mediating neurotoxic signalling by sensitizing cells to toxic effects of various β-sheet-rich (β) conformers of completely different origins, formed by (i) heterologous PrP, (ii) amyloid β-peptide, (iii) yeast prion proteins or (iv) designed β-peptides. Toxic signalling via PrP(C) requires the intrinsically disordered N-terminal domain (N-PrP) and the GPI anchor of PrP. We found that the N-terminal domain is important for mediating the interaction of PrP(C) with β-conformers. Interestingly, a secreted version of N-PrP associated with β-conformers and antagonized their toxic signalling via PrP(C). Moreover, PrP(C)-mediated toxic signalling could be blocked by an NMDA receptor antagonist or an oligomer-specific antibody. Our study indicates that PrP(C) can mediate toxic signalling of various β-sheet-rich conformers independent of infectious prion propagation, suggesting a pathophysiological role of the prion protein beyond of prion diseases.
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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.