부산대학교 도서관

Prion diseases are a group of invariably fatal neurodegenerative disorders that include Creutzfeldt–Jakob disease in humans, scrapie in sheep and goats, and bovine spongiform encephalopathy in cattle. The infectious agent or prion is largely composed of an abnormal isoform (PrP) of a host encoded normal cellular protein (PrP). The conversion of PrP to PrP is a dynamic process and, for reasons that are not clear, the distribution of spongiform change and PrP deposition varies among prion strains. An obvious explanation for this would be that the transformation efficiency in any given brain region depends on favourable interactions between conformations of PrP and the prion strain being propagated within it. However, identification of specific PrP conformations has until now been hampered by a lack of suitable panels of antibodies that discriminate PrP subspecies under native conditions. In this study, we show that monoclonal antibodies raised against recombinant human prion protein folded into α or β conformations exhibit striking heterogeneity in their specificity for truncations and glycoforms of mouse brain PrP. We then show that some of these PrP isoforms are expressed differentially in certain mouse brain regions. This suggests that variation in the expression of PrP conformations in different brain regions may dictate the pattern of PrP deposition and vacuolation, characteristic for different prion strains.