Interaction of Prion Protein with Small Highly Structured RNAs: Detection and Characterization of PrP-Oligomers
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- Vasan, S., Mong, P.Y. & Grossman, A. Neurochem Res (2006) 31: 629. doi:10.1007/s11064-006-9063-5
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Conformational modification of normal prion protein (PrPc) to protease-resistant, β-sheet rich, aggregates (PrPsc) is commonly accepted cause for prion diseases. On the other hand, several studies in recent years implicate soluble, protease-sensitive, oligomers of PrPc in neuronal damage. Previously, our group has shown that small, highly structured RNAs (shsRNAs), in conjunction with a serum factor, facilitated the conversion of hrPrP to a protease resistant, high molecular weight isoform. In the current study we demonstrate that shsRNAs, in the absence of the serum factor, generate soluble, protease-sensitive, and potentially toxic oligomers of ovrPrP. We have isolated a 500 kD oligomer by size exclusion chromatography of the reaction mixture and identified the accessible epitopes. The soluble PrP-oligomers were present in enhanced amounts in scrapie infected sheep brain and treating extracts of normal sheep brain with shsRNA resulted in oligomerization of endogenous PrP. Isolation, characterization of PrP-oligomers and their possible implication in prion diseases is discussed.