NR AWIW
AU Legname,G.; Nguyen,H.O.B.; Cohen,F.E.; DeArmond,S.J.; Prusiner,S.B.
TI Less stable prions replicate more rapidly in mice
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Oral sessions ORAL-15
PT Konferenz-Vortrag
AB Infectious synthetic prions obtained from purified recombinant prion protein of mouse residues 89 to 230 [MoPrP(89-230)] show increased conformational stability when inoculated into transgenic (Tg) mice expressing PrP of the same sequence. These novel Mo synthetic prion strains (MoSP) were also characterized by unique neuropathologic changes in inoculated Tg or non-Tg mice. On passaging of strain MoSP1, two strains emerged with incubation times differing by nearly 100 days. Using conformational-stability assays, we determined the GdnHCl concentration required to denature 50% of the PrPsc molecules. The [GdnHCl]1/2 values were 2.9 M and 3.7 M for the shorter- and longer-incubating prion strains, respectively. Intrigued by this finding, we measured the conformational stabilities of many prion isolates from synthetic and naturally occurring sources. When the incubation times were plotted as a function of the [GdnHCl]1/2 values, a linear relationship was found. Unexpectedly, our investigation indicates that less stable prions replicate more rapidly than stable prions.
AD G. Legname: Institute for Neurodegenerative Diseases, Department of Neurology, University of California, San Francisco, CA, USA; F.E. Cohen: Institute for Neurodegenerative Diseases, Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA; S.J. de Armond: Institute for Neurodegenerative Diseases, Department of Pathology, University of California, San Francisco, CA, USA; H.-O.B. Nguyen: Institute for Neurodegenerative Diseases, University of California, San Francisco, CA, USA; S.B. Prusiner: Institute for Neurodegenerative Diseases, Departments of Neurology, Biochemistry and Biophysics, University of California, San Francisco, CA, USA. E-mail: glegname@ind.ucsf.edu
SP englisch
PO Italien