TY - JOUR
T1 - Evidence for the conformation of the pathologic isoform of the prion protein enciphering and propagating prion diversity
AU - Telling, Glenn C.
AU - Parchi, Piero
AU - DeArmond, Stephen J.
AU - Cortelli, Pietro
AU - Montagna, Pasquale
AU - Gabizon, Ruth
AU - Mastrianni, James
AU - Lugaresi, Elio
AU - Gambetti, Pierluigi
AU - Prusiner, Stanley B.
PY - 1996/12/20
Y1 - 1996/12/20
N2 - The fundamental event in prion diseases seems to be a conformational change in cellular prion protein (PrP(C)) whereby it is converted into the pathologic isoform PrP(Sc). In fatal familial insomnia (FFI), the protease- resistant fragment of PrP(Sc) 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 PrP(Sc) fragment, whereas extracts from the brains of familial and sporadic Creutzfeldt-Jakob disease patients produced the 21-kilodalton PrP(Sc) fragment in these mice. The results presented indicate that the conformation of PrP(Sc) functions as a template in directing the formation of nascent PrP(Sc) and suggest a mechanism to explain strains of prions where diversity is encrypted in the conformation of PrP(Sc).
AB - The fundamental event in prion diseases seems to be a conformational change in cellular prion protein (PrP(C)) whereby it is converted into the pathologic isoform PrP(Sc). In fatal familial insomnia (FFI), the protease- resistant fragment of PrP(Sc) 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 PrP(Sc) fragment, whereas extracts from the brains of familial and sporadic Creutzfeldt-Jakob disease patients produced the 21-kilodalton PrP(Sc) fragment in these mice. The results presented indicate that the conformation of PrP(Sc) functions as a template in directing the formation of nascent PrP(Sc) and suggest a mechanism to explain strains of prions where diversity is encrypted in the conformation of PrP(Sc).
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U2 - 10.1126/science.274.5295.2079
DO - 10.1126/science.274.5295.2079
M3 - Article
C2 - 8953038
AN - SCOPUS:12644272790
VL - 274
SP - 2079
EP - 2082
JO - Science
JF - Science
SN - 0036-8075
IS - 5295
ER -