PrPSc

Prions—protein particles that lack nucleic acid— cause fatal transmissible spongiform encephalopathies such as Creutzfeldt-Jakob disease, scrapie, and bovine spongiform encephalopathy. Prion diseases involve an altered secondary-tertiary strucmre of a namrally occurring protein, PrPc. When PrPc interacts with its pathologic isoform PrPSc, its conformation is transformed from a predominantly a-helical strucmre to the P-sheet strucmre characteristic of PrPSc. 

Monleon E, Monzon M, Hortells P, et al. Detection of PrPsc in samples presenting a very advanced degree of autolysis (BSE liquid state) by immunocytochemistry. J. Histochem. Cytochem. 2003 51 15-18. 

Prion propagation involves conversion of PrPc to PrPSc 795... 

PrPSc has a predominantly fl-sheet conformation 797 In vitro conversion of PrPc to alternative conformations 798... 

Distinct PrPSc types are seen in human prion disease 799... 

How pathogenic mutations in PRNP cause prion disease has yet to be resolved. However, in most cases the mutation is thought to lead to an increased tendency of PrPc to form PrPSc, although there is evidence to suggest that this may not be solely attributable to decreased thermodynamic stability of mutated PrPc. Experimentally manipulated mutations of the prion gene can lead to spontaneous neurodegeneration without the formation... 

A wide body of data now supports the idea that infectious prions consist principally or entirely of an abnormal iso form of PrP. Disease associated PrP, designated PrPSc, is derived from PrPc by a post-translational mechanism and neither amino acid sequencing nor systematic study of known covalent post-translational modifications have shown any consistent differences between PrPc and PrIJSt [5,20]. 

All three of these predictions from this minimal model are manifest in the etiology of prion disease an inversely proportional relationship between PrPc expression and prion incubation period in transgenic mice predisposition by relatively subtle mutations in the protein sequence and a requirement for molecular homogeneity between PrPSc and PrPc for efficient prion propagation [4, 5, 20]. It is clear that a full understanding of prion propagation will require knowledge both of the structure of PrPc and PrPSc and of the mechanism of conversion between them. 

PrPres Prion protein that is partially resistant against proteinase K digest (in most cases equal to PrPSc or PrP27-30)... 

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