Journal
NATURE
Volume 437, Issue 7056, Pages 257-261Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature03989
Keywords
-
Categories
Funding
- Intramural NIH HHS Funding Source: Medline
- NIAID NIH HHS [Z01 AI000580-16] Funding Source: Medline
Ask authors/readers for more resources
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(1,2). Abnormal deposits in TSEs are rich in PrPres, a protease-resistant form of the PrP protein with the ability to convert the normal, protease-sensitive form of the protein (PrPsen) into PrPres (ref. 3). TSEs can be transmitted between organisms by an enigmatic agent (prion) that contains PrPres (refs 4 and 5). To evaluate systematically the relationship between infectivity, converting activity and the size of various PrPres-containing aggregates, PrPres 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 <= 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available