The most infectious prion protein particles
Open accessAbstract
Neurodegenerative diseases such as Alzheimer's, Parkinson's and the transmissible spongiform encephalopathies (TSEs) are characterized by abnormal protein deposits, often with large amyloid fibrils. However, questions have arisen as to whether such fibrils or smaller subfibrillar oligomers are the prime causes of disease. Abnormal deposits in TSEs are rich in PrP(res), a protease-resistant form of the PrP protein with the ability to convert the normal, protease-sensitive form of the protein (PrP(sen)) into PrP(res) (ref. 3). TSEs can be transmitted between organisms by an enigmatic agent (prion) that contains PrP(res) (refs 4 and 5). To evaluate systematically the relationship between infectivity, converting activity and the size of various PrP(res)-containing aggregates, PrP(res) was partially disaggregated, fractionated by size and analysed by light scattering and non-denaturing gel electrophoresis. Our analyses revealed that with respect to PrP content, infectivity and converting activity peaked markedly in 17-27-nm (300-600 kDa) particles, whereas these activities were substantially lower in large fibrils and virtually absent in oligomers of < or =5 PrP molecules. These results suggest that non-fibrillar particles, with masses equivalent to 14-28 PrP molecules, are the most efficient initiators of TSE disease.
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Soluble Aβ seeds could serve as informative biomarkers in bodily fluids.
“Because the most potent Aβ seeds, like prions97, appear to be relatively small54, soluble Aβ seeds could serve as informative biomarkers in bodily fluids.”
From Pathogenic protein seeding in Alzheimer disease and other neurodegenerative disorders (2011) · cites this paper as [97]
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- Authors
- Silveira, J. R., Raymond, G. J., Hughson, A. G., Race, R. E., Sim, V. L., Hayes, S. F., & Caughey, B.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Caughey, Byron
- Venue
- Nature
- Published
- 2005-09
- Volume
- 437
- Issue
- 7056
- Pages
- 257-261
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC1513539
- OpenAlex
- W2030072508
- Cited by
- 899
- References
- 30
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 18 · 2023: 15 · 2022: 16 · 2021: 32 · 2020: 30 · 2019: 32 · 2018: 23 · 2017: 39 · 2016: 57 · 2015: 37 · 2014: 48 · 2013: 64 · 2012: 68
- FWCI
- 26.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (Z01AI000580)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- prion infectivity, prion disease, Creutzfeldt-Jakob disease, oligomer size, amyloid fibrils, protein misfolding, domain swapping, neurodegenerative diseases, Alzheimer's disease
- MeSH terms
- Animals, Brain, Electrophoresis, Polyacrylamide Gel, Chemical Fractionation, Cricetinae, Molecular Weight, Scattering, Radiation, Immunoblotting, Prion Diseases, PrPSc Proteins, Protein Structure, Quaternary, Microscopy, Electron, Transmission
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