In human and animal transmissible spongiform encephalopathies (TSEs) or prion disorders, biochemical analysis of disease-associated prion protein (PrPTSE) is a first-line approach for large scale routine testing and for a rapid molecular typing. This characterization is based on conformational properties of PrPTSE enciphered in its secondary and tertiary structures and on glycosylation profile. Several biochemical approaches are helpful in distinguishing PrPTSE forms in human prion diseases. In particular, in sporadic Creutzfedlt-Jakob disease (CJD), PrPTSE is characterized by two main glycotypes conventionally named PrPTSE type 1 and PrPTSE type 2 based on the apparent gel migration at 19 kDa and 17.5 kDa and glycofrom ratio. Further, there are PrPTSE low molecular weight fragments which correlate to distinct phenotypes of sCJD. Finally, by using two-dimensional PAGE analysis, which separates PrPTSE on both isoelectric point and molecular size, we were able to detect two distinct migration pattern in PrPTSE type 2, one in subjects with MM at codon 129 and another in MV, VV. We here provide an extensive PrPTSE biochemical analysis in humans and animals affected with prion disorders. Further, we showed that PrPTSE glycotypes observed in CJD shared similarities with PrPTSE in bovine spongiform encephalopathies (BSEs). These signature similarities obtained by a biochemical analysis had been further confirmed by experimental transmission.
Part of the book: Prion