NR AGED
AU Kaneko,K.; Ball,H.L.; Wille,H.; Zhang,H.; Groth,D.; Torchia,M.; Tremblay,P.; Safar,J.G.; Prusiner,S.B.; DeArmond,S.J.; Baldwin,M.A.; Cohen,F.E.
TI A synthetic peptide initiates Gerstmann-Sträussler-Scheinker (GSS) disease in transgenic mice
QU Journal of Molecular Biology 2000 Jan 28; 295(4): 997-1007
PT journal article
AB The molecular basis of the infectious, inherited and sporadic forms of prion diseases is best explained by a conformationally dimorphic protein that can exist in distinct normal and disease-causing isoforms. We identified a 55-residue peptide of a mutant prion protein that can be refolded into at least two distinct conformations. When inoculated intracerebrally into the appropriate transgenic mouse host, 20 of 20 mice receiving the beta-form of this peptide developed signs of central nervous system dysfunction at approximately 360 days, with neurohistologic changes that are pathognomonic of Gerstmann-Sträussler-Scheinker disease. By contrast, eight of eight mice receiving a non-beta-form of the peptide failed to develop any neuropathologic changes more than 600 days after the peptide injections. We conclude that a chemically synthesized peptide refolded into the appropriate conformation can accelerate or possibly initiate prion disease.
MH Amino Acid Sequence; Animal; Brain/drug effects/*pathology; Gerstmann-Sträussler-Scheinker Disease/*genetics/pathology/physiopathology; Human; Mice; Mice, Transgenic; Molecular Sequence Data; Peptide Fragments/administration & dosage/*chemistry/toxicity; Prions/chemistry/*genetics; Protein Conformation; Protein Folding; Protein Structure, Secondary; Scrapie/pathology; Spectroscopy, Fourier Transform Infrared; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.
AD Institute for Neurodegenerative Diseases, Department of Neurology, University of California, San Francisco, 94143, USA
SP englisch
PO England