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

@article{citeulike:3658801, 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 '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 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.}, author = {Kellershohn, N. and Laurent, M.}, citeulike-article-id = {3658801}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/9729459}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=9729459}, day = {15}, issn = {0264-6021}, journal = {The Biochemical journal}, keywords = {diseases, kinetic, prion, transmission}, month = {September}, pages = {539--545}, posted-at = {2008-11-22 03:51:15}, priority = {2}, title = {Species barrier in prion diseases: a kinetic interpretation based on the conformational adaptation of the prion protein.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/9729459}, volume = {334 ( Pt 3)}, year = {1998} }

TY - JOUR ID - citeulike:3658801 L3 - citeulike-article-id:3658801 N2 - 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 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. JF - The Biochemical journal SN - 0264-6021 EP - 545 TI - Species barrier in prion diseases: a kinetic interpretation based on the conformational adaptation of the prion protein. VL - 334 ( Pt 3) SP - 539 KW - diseases KW - kinetic KW - prion KW - transmission AU - Kellershohn, N AU - Laurent, M PY - 1998/09/15/ UR - http://view.ncbi.nlm.nih.gov/pubmed/9729459 ER -