NR ASXY
AU Silveira,J.R.; Raymond,G.J.; Hughson,A.G.; Race,R.E.; Sim,V.L.; Hayes,S.F.; Caughey,B.W.
TI The most infectious prion protein particles
QU Nature 2005 Sep 8; 437(7056): 257-61
PT journal article
AB 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 PrPres, a protease-resistant form of the PrP protein with the ability to convert the normal, protease-sensitive form of the protein (PrP(sen)) 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 < 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.
IN Die Autoren fraktionierten PrPsc nach Größen und untersuchten unter anderem die Infektiosität dieser Fraktionen. Die größte Infektiosität besaß die Fraktion der anscheinend nicht fibrillären Aggregate aus 14-28 PrPsc-Molekülen. Bei Aggregaten mit maximal 5 PrPsc-Molekülen lag die Infektiosität unter der Nachweisgrenze, aber auch längere Fibrillen waren deutlich weniger infektiös.
MH Animals; Brain; Chemical Fractionation; Electrophoresis, Polyacrylamide Gel; Hamsters; Immunoblotting; Microscopy, Electron, Transmission; Molecular Weight; PrPsc Proteins/*chemistry/isolation &; purification/*pathogenicity/ultrastructure; Prion Diseases/*metabolism/*transmission; Protein Structure, Quaternary; Research Support, N.I.H., Intramural; Scattering, Radiation
AD Jay R. Silveira, Gregory J. Raymond, Andrew G. Hughson, Richard E. Race, Valerie L. Sim, Byron Caughey, Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA; Stanley F. Hayes, Electron Microscopy Core Facility, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA
SP englisch
PO England