Species barrier in prion diseases: a kinetic interpretation based on the conformational adaptation of the prion protein

被引:7
|
作者
Kellershohn, N [1 ]
Laurent, M [1 ]
机构
[1] Univ Paris Sud, Serv Imagerie Cellulaire, URA D2227 CNRS, Ctr Orsay, F-91405 Orsay, France
关键词
D O I
10.1042/bj3340539
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Prion diseases are thought to result from the conformational change of the normal cellular prion protein to a pathogenic protease-resistant isoform. However, brain extracts not containing the protease-resistant isoform of the prion protein can be infectious following interspecies transmission. The 'protein-only' hypothesis of pathogenesis is extended to provide possible explanations which could be interpreted in terms of a different infectious agent. It is proposed that normal cellular protein (PrPC) may be transformed into a form (PrP*) that is conformationally distinct from the host-specific abnormal isoform (PrPSc). In infection from a heterologous donor, the dimeric forms of heterologous PrPSc, which may catalyse the formation: of host PrP* from PrPC, host PrP* and host PrPSc are all considered to be capable of catalysing, to some extent, the conversion of PrPC into PrPSc. However. depending on the species involved, PrP* may, or may not, be pathogenic, and may. or map not, be sensitive to proteolysis. It is shown: by numerical integration of the differential rate equations derived from this model, that a strain map be stabilized after two or three passages through a different species and that transmission might occur in the absence of detectable protease-resistant prion protein. The natural transmission of scrapie to cattle is discussed in relation to the model.
引用
收藏
页码:539 / 545
页数:7
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