NR AVRV
AU Yuan,J.; Xiao,X.; McGeehan,J.; Dong,Z.; Cali,I.; Fujioka,H.; Kong,Q.; Kneale,G.; Gambetti,P.; Zou,W.Q.
TI Insoluble aggregates and protease-resistant conformers of prion protein in uninfected human brains
QU The Journal of Biological Chemistry 2006 Nov 17; 281(46): 34848-58
PT journal article; research support, n.i.h., extramural; research support, non-u.s. gov't; research support, u.s. gov't, p.h.s.
AB Aggregated prion protein (PrPsc), which is detergent-insoluble and partially proteinase K (PK)-resistant, constitutes the major component of infectious prions that cause a group of transmissible spongiform encephalopathies in animals and humans. PrPsc derives from a detergent-soluble and PK-sensitive cellular prion protein (PrPc) through an alpha-helix to beta-sheet transition. This transition confers on the PrPsc molecule unique physicochemical and biological properties, including insolubility in nondenaturing detergents, an enhanced tendency to form aggregates, resistance to PK digestion, and infectivity, which together are regarded as the basis for distinguishing PrPsc from PrPc. Here we demonstrate, using sedimentation and size exclusion chromatography, that small amounts of detergent-insoluble PrP aggregates are present in uninfected human brains. Moreover, PK-resistant PrP core fragments are detectable following PK treatment. This is the first study that provides experimental evidence supporting the hypothesis that there might be silent prions lying dormant in normal human brains.
MH Animals; Brain/*metabolism/pathology; Cattle; Cricetinae; Humans; Peptide Hydrolases/*metabolism; Prions/*chemistry/*metabolism; Solubility
AD Department of Pathology and National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, Ohio 44106, USA
SP englisch
PO USA