ArticleScience advances2016
Copper-induced structural conversion templates prion protein oligomerization and neurotoxicity.
Article in Science advances, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 51 citations in OpenAlex.
- Different folding mechanisms in prion proteins from mammals with different disease susceptibility observed at the single-molecule level.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Synthesis and anti-prion aggregation activity of acylthiosemicarbazide analogues.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Prion Protein Octarepeat Domain Forms Transient β-Sheet Structures upon Residue-Specific Binding to Cu(II) and Zn(II) Ions.Biochemistry · 2023Article
- Structural and dynamical determinants of a β-sheet-enriched intermediate involved in amyloid fibrillar assembly of human prion protein.Chemical science · 2022Article
- Multiparametric High-Content Cell Painting Identifies Copper Ionophores as Selective Modulators of Esophageal Cancer Phenotypes.ACS chemical biology · 2022Article
- Melatonin: Regulation of Prion Protein Phase Separation in Cancer Multidrug Resistance.Molecules (Basel, Switzerland) · 2022Review
- Size-Specific Copper Nanoparticle Cytotoxicity Varies between Human Cell Lines.International journal of molecular sciences · 2021Article
- The Effects of Divalent Cation-Chelated Prion Fibrils on the Immune Response of EOC 13.31 Microglia Cells.Cells · 2020Article
- Using NMR spectroscopy to investigate the role played by copper in prion diseases.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2020Review
- Enhanced differentiation of human dopaminergic neuronal cell model for preclinical translational research in Parkinson's disease.Biochimica et biophysica acta. Molecular basis of disease · 2020Article
- A probable role of copper in the comorbidity in Wilson's and Creutzfeldt-Jakob's Diseases: a case report.Virology journal · 2020Article
- Review
- Mutations in Prion Protein Gene: Pathogenic Mechanisms in C-Terminal vs. N-Terminal Domain, a Review.International journal of molecular sciences · 2019Review
- Effects of nano-copper on maize yield and inflammatory response in mice.Iranian journal of basic medical sciences · 2019Article
- Oxidative and Inflammatory Events in Prion Diseases: Can They Be Therapeutic Targets?Current aging science · 2019Review
- Copper signalling: causes and consequences.Cell communication and signaling : CCS · 2018Review
- Article
- Graphene Oxide Quantum Dots Reduce Oxidative Stress and Inhibit Neurotoxicity In Vitro and In Vivo through Catalase-Like Activity and Metabolic Regulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2018Article
- Improving estimation of kinetic parameters in dynamic force spectroscopy using cluster analysis.The Journal of chemical physics · 2018Article
- Manganese exposure induces neuroinflammation by impairing mitochondrial dynamics in astrocytes.Neurotoxicology · 2018Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Prion protein (PrP) misfolding and oligomerization are key pathogenic events in prion disease. Copper exposure has been linked to prion pathogenesis; however, its mechanistic basis is unknown. We resolve, with single-molecule precision, the molecular mechanism of Cu(2+)-induced misfolding of PrP under physiological conditions. We also demonstrate that misfolded PrPs serve as seeds for templated formation of aggregates, which mediate inflammation and degeneration of neuronal tissue. Using a single-molecule fluorescence assay, we demonstrate that Cu(2+) induces PrP monomers to misfold before oligomer assembly; the disordered amino-terminal region mediates this structural change. Single-molecule force spectroscopy measurements show that the misfolded monomers have a 900-fold higher binding affinity compared to the native isoform, which promotes their oligomerization. Real-time quaking-induced conversion demonstrates that misfolded PrPs serve as seeds that template amyloid formation. Finally, organotypic slice cultures show that misfolded PrPs mediate inflammation and degeneration of neuronal tissue. Our study establishes a direct link, at the molecular level, between copper exposure and PrP neurotoxicity.
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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.