NR AAVL
AU Aucouturier,P.; Kascsak,R.J.; Frangione,B.; Wisniewski,T.
TI Biochemical and conformational variability of human prion strains in sporadic Creutzfeldt-Jakob disease
QU Neuroscience Letters 1999 Oct 15; 274(1): 33-6
PT journal article
AB The pathogenesis of prion (PrP) diseases is thought to be related to conformational changes of a normal cellular protein, PrPc, into a protease resistant protein called PrPsc, which is infectious by itself. A difficulty with this 'protein only' hypothesis is the existence of numerous PrP strains, that require PrPsc to have multiple conformations. Sporadic Creutzfeldt-Jakob disease (CJD), which accounts for nearly 80% of human prionoses, was reported to include at least two 'strains' termed types 1 and 2 which differ by electrophoretic patterns of their proteinase K (PK)-resistant fragments (PrP27-30). We have analyzed the biochemical and structural properties of PrPsc and PrP27-30 isolates from six sporadic CJD patients. Fourier transform-infra-red spectroscopy, PrP27-30 glycosylation patterns and studies of PK sensitivity revealed a striking heterogeneity. Furthermore, one isolate yielded a PrP27-30 fragment with a lower mobility clearly different from previously described sporadic CJD types. Although the average beta-sheet content was higher among type 1 isolates, there was overlap between the two types. Our study suggests that human sporadic CJD-related prions display a significant heterogeneity.
MH Aged; Blotting, Western; Creutzfeldt-Jakob Syndrome/*metabolism; Female; Glycosylation; Human; Male; Middle Age; Neocortex/*chemistry; PrP 27-30 Protein/analysis/*chemistry/isolation & purification; PrPsc Proteins/analysis/*chemistry/isolation & purification; Protein Conformation; Protein Structure, Secondary; Spectroscopy, Fourier Transform Infrared; Support, U.S. Gov't, P.H.S.
AD Department of Pathology, New York University School of Medicine, NY 10016, USA
SP englisch
PO Irland