Evidence for the conformation of the pathologic isoform of the prion protein enciphering and propagating prion diversity

Science
G C TellingS B Prusiner

Abstract

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.

References

Feb 13, 1992·The New England Journal of Medicine·R MedoriP Cortelli
Aug 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·A TaraboulosS B Prusiner
Oct 1, 1992·Neurology·R B PetersenW W Pendlebury
Feb 1, 1992·The Journal of General Virology·R A Bessen, R F Marsh
Jun 14, 1991·Science·S B Prusiner
Dec 1, 1987·Journal of Virology·R J KascsakH Diringer
Jan 1, 1987·The Journal of General Virology·M E Bruce, A G Dickinson
Jul 20, 1973·Science·C B Anfinsen
Jan 1, 1973·Journal of Comparative Pathology·H Fraser, A G Dickinson
Jul 1, 1968·Journal of Comparative Pathology·A G DickinsonH Fraser
Dec 1, 1983·Cell·S B PrusinerG G Glenner
Aug 3, 1995·Nature·J TateishiD C Gajdusek
Dec 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·K M PanF E Cohen
Mar 29, 1994·Proceedings of the National Academy of Sciences of the United States of America·L MonariB Ghetti
Apr 22, 1994·Science·F E CohenS B Prusiner
Oct 11, 1994·Proceedings of the National Academy of Sciences of the United States of America·G C TellingS B Prusiner
Jul 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·S J DeArmondS B Prusiner
Aug 29, 1996·Nature·R M AndersonG A Wells

❮ Previous
Next ❯

Citations

Jan 12, 2002·Reviews in Medical Virology·P D Griffiths
Aug 10, 2010·Acta Neuropathologica·Jonathan D F Wadsworth, John Collinge
Nov 9, 2010·Acta Neuropathologica·Pierluigi GambettiWitold K Surewicz
Jun 27, 2013·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Sarah K Kaufman, Marc I Diamond
Mar 2, 2005·Sleep Medicine Reviews·Peretz Lavie
Dec 9, 2003·Trends in Microbiology·Andrew F Hill, John Collinge
Nov 5, 2002·Clinical Biochemistry·Hassan M E Azzazy, W Edward Highsmith
Dec 10, 2002·Mechanisms of Ageing and Development·Yanming Xing, Keiichi Higuchi
Aug 10, 1999·Lancet·J Collinge
Mar 14, 2002·Brain Research. Brain Research Reviews·Ollivier Milhavet, Sylvain Lehmann
Jul 1, 1997·Trends in Genetics : TIG·R Gabizon, A Taraboulos
Dec 31, 2002·Toxicology·Stephen J DeArmond, Essia Bouzamondo
Jun 30, 1997·Biophysical Chemistry·D Riesner
Oct 19, 2000·Neuroscience Letters·L Manuelidis, Z Yun Lu
Dec 1, 1998·Neuroscience Letters·A F HillJ Collinge
Oct 1, 1998·Cellular Signalling·A SchlegelM P Lisanti
Aug 28, 1998·Current Opinion in Biotechnology·V Daggett
Mar 21, 1998·Current Opinion in Biotechnology·T W Rademacher
Feb 7, 1998·Current Opinion in Neurobiology·C Weissmann, A Aguzzi
Feb 1, 1997·Current Opinion in Structural Biology·P M HarrisonF E Cohen
Apr 1, 1997·Trends in Cell Biology
Feb 7, 2001·Trends in Microbiology·R I Carp
May 1, 1997·Trends in Biochemical Sciences·R BrasseurM Rosseneu
Sep 25, 2002·Microbes and Infection·Lev G Goldfarb
Jun 22, 2000·Molecular Medicine Today·F E Cohen
Oct 18, 2002·Trends in Molecular Medicine·Thierry Baron
Jul 10, 2003·Lancet Neurology·John CollingePeter Rudge
Feb 28, 2002·Comptes rendus biologies·James W Ironside
Feb 28, 2002·Comptes rendus biologies·Odile KellermannSophie Mouillet-Richard
Jul 23, 2011·Biochemistry·Justin R PiroSurachai Supattapone
Dec 14, 2012·Biomacromolecules·James M McCarthyMark S Rogers
Oct 15, 1998·Nature Medicine·A Aguzzi
Oct 15, 1998·Nature Medicine·J SafarS B Prusiner
Aug 14, 1998·Nature Biotechnology·D J Goldstein
Feb 14, 1998·Nature Genetics·G A Carlson
Jun 23, 2007·Nature Reviews. Molecular Cell Biology·Adriano AguzziMagdalini Polymenidou
Oct 21, 2004·Nature Reviews. Microbiology·Charles Weissmann
Sep 29, 2011·Nature Reviews. Microbiology·David W Colby, Stanley B Prusiner

❮ Previous
Next ❯

Related Concepts

Related Feeds

Bovine Spongiform Encephalopathy

Bovine spongiform encephalopathy is a neurodegenerative disease belonging to the transmissible spongiform encephalopathies, a group of diseases including sheep scrapie and human Creutzfeldt-Jakob disease. Here is the latest research.

Bovine Spongiform Encephalopathy (MDS)

Bovine spongiform encephalopathy is a neurodegenerative disease belonging to the transmissible spongiform encephalopathies, a group of diseases including sheep scrapie and human Creutzfeldt-Jakob disease. Here is the latest research.