Biochemical and conformational variability of human prion strains in sporadic Creutzfeldt-Jakob disease

NEUROSCIENCE LETTERS

卷:274

Article

Aucouturier, P ; Kascsak, RJ ; Frangione, B ; Wisniewski, T

关键词: prion;    Creutzfeldt-Jakob disease;    conformation;    PrP;    strains;    Fourier transform infra-red spectroscopy;   

DOI  :  10.1016/S0304-3940(99)00659-X

来源: Elsevier

【 摘 要 】

The pathogenesis of prion (PrP) diseases is thought to be related to conformational changes of a normal cellular protei n, PrPC, into a protease resistant protei n ca I led PrPSc, wh ich 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 hu man sporadic CJD-related prions display a significant heterogeneity. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.

【 授权许可】

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