The molecular pathology of CJD: old and new variants.
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.
Jackson
G S
GS
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
Collinge
J
J
D000818:Animals; D001923:Brain Chemistry; D016923:Cell Death; D007562:Creutzfeldt-Jakob Syndrome / Q000145:classification / Q000235:genetics* / Q000473:pathology; D020566:Dendritic Cells, Follicular / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D008957:Models, Genetic; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism; D018620:PrPSc Proteins / Q000235:genetics / Q000378:metabolism; D011328:Prions / Q000235:genetics* / Q000378:metabolism; D011487:Protein Conformation
D018621:PrPC Proteins; D018620:PrPSc Proteins; D011328:Prions