@article {785,
	title = {Species barrier in prion diseases: a kinetic interpretation based on the conformational adaptation of the prion protein},
	journal = {Biochem J},
	volume = {334 ( Pt 3)},
	year = {1998},
	note = {Kellershohn, N Laurent, M Research Support, Non-U.S. Gov{\textquoteright}t England The Biochemical journal Biochem J. 1998 Sep 15;334 ( Pt 3):539-45.},
	month = {Sep 15},
	pages = {539 - 45},
	edition = {36046},
	abstract = {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 {\textquoteright}protein-only{\textquoteright} 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 may not, be sensitive to proteolysis. It is shown, by numerical integration of the differential rate equations derived from this model, that a strain may 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.},
	keywords = {*Models, Biological, Animals, Cattle, Dimerization, Endopeptidases / pharmacology, Humans, Kinetics, Prion Diseases / etiology / *metabolism / *transmission, Prions / *chemistry / metabolism / *pathogenicity, Protein Conformation, PrPC Proteins / chemistry / metabolism, PrPSc Proteins / chemistry / metabolism / pathogenicity, Species Specificity, Thermodynamics},
	issn = {0264-6021 (Print) 0264-6021 (Linking)},
	author = {Kellershohn,N. and Laurent,M.}
}
