ArticleProceedings of the National Academy of Sciences of the United States of America2012
Highly neurotoxic monomeric α-helical prion protein.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 50 citations in OpenAlex.
- Stereotaxic Delivery of M1000 Prions to the Hippocampus Induces Related Behavioural and Cognitive Changes Consistent with Acute Neurotoxic Effects.Molecular neurobiology · 2025Article
- 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
- Structural insights into the molecular recognition of integrin αVβ3 by RGD-containing ligands: The role of the specificity-determining loop (SDL).bioRxiv : the preprint server for biology · 2024Article
- The role of astrocytes in prion-like mechanisms of neurodegeneration.Brain : a journal of neurology · 2022Review
- Protein mimetic amyloid inhibitor potently abrogates cancer-associated mutant p53 aggregation and restores tumor suppressor function.Nature communications · 2021Article
- Alpha-synuclein modulates dopamine neurotransmission.Journal of chemical neuroanatomy · 2017Review
- Prion protein inhibits fast axonal transport through a mechanism involving casein kinase 2.PloS one · 2017Article
- Article
- The Pathogenic A116V Mutation Enhances Ion-Selective Channel Formation by Prion Protein in Membranes.Biophysical journal · 2016Article
- A cationic tetrapyrrole inhibits toxic activities of the cellular prion protein.Scientific reports · 2016Article
- Prions and Protein Assemblies that Convey Biological Information in Health and Disease.Neuron · 2016Review
- Prion Infectivity Plateaus and Conversion to Symptomatic Disease Originate from Falling Precursor Levels and Increased Levels of Oligomeric PrPSc Species.Journal of virology · 2015Article
- Prion-induced neurotoxicity: Possible role for cell cycle activity and DNA damage response.World journal of virology · 2015Review
- Neuronal death induced by misfolded prion protein is due to NAD+ depletion and can be relieved in vitro and in vivo by NAD+ replenishment.Brain : a journal of neurology · 2015Article
- Unfolded protein response-induced ERdj3 secretion links ER stress to extracellular proteostasis.The EMBO journal · 2015Article
- Article
- Could α-synuclein amyloid-like aggregates trigger a prionic neuronal invasion?BioMed research international · 2015Review
- Cytosolic PrP can participate in prion-mediated toxicity.Journal of virology · 2014Article
- Complex proteinopathy with accumulations of prion protein, hyperphosphorylated tau, α-synuclein and ubiquitin in experimental bovine spongiform encephalopathy of monkeys.The Journal of general virology · 2014Article
- Thermodynamic characterization of the unfolding of the prion protein.Biophysical journal · 2014Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Prion diseases are infectious and belong to the group of protein misfolding neurodegenerative diseases. In these diseases, neuronal dysfunction and death are caused by the neuronal toxicity of a particular misfolded form of their cognate protein. The ability to specifically target the toxic protein conformer or the neuronal death pathway would provide powerful therapeutic approaches to these diseases. The neurotoxic forms of the prion protein (PrP) have yet to be defined but there is evidence suggesting that at least some of them differ from infectious PrP (PrP(Sc)). Herein, without making an assumption about size or conformation, we searched for toxic forms of recombinant PrP after dilution refolding, size fractionation, and systematic biological testing of all fractions. We found that the PrP species most neurotoxic in vitro and in vivo (toxic PrP, TPrP) is a monomeric, highly α-helical form of PrP. TPrP caused autophagy, apoptosis, and a molecular signature remarkably similar to that observed in the brains of prion-infected animals. Interestingly, highly α-helical intermediates have been described for other amyloidogenic proteins but their biological significance remains to be established. We provide unique experimental evidence that a monomeric α-helical form of an amyloidogenic protein represents a cytotoxic species. Although toxic PrP has yet to be purified from prion-infected brains, TPrP might be the equivalent of one highly neurotoxic PrP species generated during prion replication. Because TPrP is a misfolded, highly neurotoxic form of PrP reproducing several features of prion-induced neuronal death, it constitutes a useful model to study PrP-induced neurodegenerative mechanisms.
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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.