NR ALPJ
AU Telling,G.C.; Parchi,P.; DeArmond,S.J.; Cortelli,P.; Montagna,P.; Gabizon,R.; Mastrianni,J.A.; Lugaresi,E.; Gambetti,P.; Prusiner,S.B.
TI Evidence for the conformation of the pathologic isoform of the prion protein enciphering and propagating prion diversity
QU Science 1996 Dec 20; 274(5295): 2079-82
KI Science. 1996 Dec 20;274(5295):2010. PMID: 8984659
PT journal article
AB The fundamental event in prion diseases seems to be a conformational change in cellular prion protein (PrPc) whereby it is converted into the pathologic isoform PrPsc. In fatal familial insomnia (FFI), the protease-resistant fragment of PrPsc after deglycosylation has a size of 19 kilodaltons, whereas that from other inherited and sporadic prion diseases is 21 kilodaltons. Extracts from the brains of FFI patients transmitted disease to transgenic mice expressing a chimeric human-mouse PrP gene about 200 days after inoculation and induced formation of the 19-kilodalton PrPsc fragment, whereas extracts from the brains of familial and sporadic Creutzfeldt-Jakob disease patients produced the 21-kilodalton PrPsc fragment in these mice. The results presented indicate that the conformation of PrPsc functions as a template in directing the formation of nascent PrPsc and suggest a mechanism to explain strains of prions where diversity is encrypted in the conformation of PrPsc.
MH Animal; Brain/*pathology; *Brain Chemistry; Creutzfeldt-Jakob Syndrome/metabolism/pathology; Human; Mice; Mice, Transgenic; PrPsc Proteins/analysis/*chemistry; Prion Diseases/*etiology/metabolism/pathology/transmission; Prions/*chemistry; *Protein Conformation; Protein Folding; Protein Structure, Secondary; Protein Structure, Tertiary; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.
AD Department of Neurology, University of California, San Francisco, CA 94143, USA
SP englisch
PO USA