NR AFXH
AU Jackson,G.S.; Collinge,J.
TI The molecular pathology of CJD: old and new variants.
QU Molecular Pathology 2001 Dec; 54(6): 393-9
PT journal article; review; review, tutorial
AB The study of prion disease has become an area of intense interest since experimental evidence emerged for the transmission of phenotypic variation without the involvement of a nucleic acid component. Additional impetus has come from the widespread concern that exposure to bovine spongiform encephalopathy contaminated material poses a distinct and, conceivably, a severe threat to public health in the UK and other countries. The occurrence of new variant Creutzfeldt-Jakob disease has dramatically highlighted the need for a precise understanding of the molecular basis of prion propagation. The molecular basis of prion strain diversity, previously a major challenge to the "protein only" model, can now be reconciled with propagation of infectious protein topologies. The conformational change known to be central to prion propagation, from a predominantly alpha-helical fold to one predominantly comprising beta-structure, can now be reproduced in vitro, and the ability of beta-PrP to form fibrillar aggregates provides a plausible molecular mechanism for prion propagation. Concomitantly, advances in the fundamental biology of prion disease have done much to reinforce the protein only hypothesis of prion replication.
ZR 63
MH Animal; Brain Chemistry; Cell Death; Creutzfeldt-Jakob Syndrome/classification/*genetics/pathology; Dendritic Cells, Follicular/metabolism; Human; Mice; Mice, Transgenic; Models, Animal; Models, Genetic; Neurons/metabolism/pathology; PrPc Proteins/genetics/metabolism; PrPsc Proteins/genetics/metabolism; Prions/*genetics/metabolism; Protein Conformation
AD MRC Prion Unit, Department of Neurogenetics, Imperial College School of Medicine at St Mary's, Norfolk Place, Paddington, London W2 1NY, UK. g.s.jackson@ic.ac.uk
SP englisch
PO England