NR ATGL
AU Head,M.W.; Yull,H.M.; Ritchie,D.L.; Langeveld,J.P.M.; van Zijderveld,F.G.; Bruce,M.E.; Ironside,J.W.
TI Multiple PrPsc Conformations in Variant Creutzfeldt-Jakob Disease
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Oral sessions ORAL-42
PT Konferenz-Vortrag
AB Molecular strain typing has come to be regarded as a powerful tool in the investigation of prion diseases. Current molecular classification systems are based on the measurement of the molecular size of the protease-resistant core fragment of the abnormal prion protein (PrPsc) and the occupancy of the two aspargine-linked glycosylation sites. These biochemical differences in conformation and glycosylation have been proposed to underlie disease phenotype and mediate heritable strain-like properties. The phenotype of variant Creutzfeldt-Jakob disease is distinct from those of other human prion diseases and the behavior of the biological agent resembles that of bovine spongiform encephalopathy. All evidence thus far presented indicates a single PrPsc molecular type in variant Creutzfeldt-Jakob disease. However, we have determined that an alternative molecular type also exists, albeit at lower levels, in the variant Creutzfeldt-Jakob disease brain. The presence of this minority molecular type is a consistent feature of the variant Creutzfeldt-Jakob disease brain and it is also found in the variant Creutzfeldt-Jakob tonsil. Moreover, the relative level of these two molecular types is maintained following transmission of variant Creutzfeldt-Jakob disease to wild-type mice. These findings suggest that molecular type is a quantitative rather than qualitative phenomenon and raise interesting questions regarding the molecular mechanism of prion replication and the relationship of PrPsc type to agent strain.
AD M.W.Head, H.M.Yull, D.L.Ritchie, J.W.Ironside, University of Edinburgh, UK; J.P.M.Langeveld, F.G.van Zijderveld, Central Institute for Animal Disease Control, Netherlands; M.E.Bruce, Institute for Animal Health, UK
SP englisch
PO Deutschland