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Interaction of prion protein with small highly structured RNAs: detection and characterization of PrP-oligomers.

Authors
  • Vasan, Sara
  • Mong, Phyllus Y
  • Grossman, Abraham
Type
Published Article
Journal
Neurochemical research
Publication Date
May 01, 2006
Volume
31
Issue
5
Pages
629–637
Identifiers
PMID: 16770734
Source
Medline
License
Unknown

Abstract

Conformational modification of normal prion protein (PrP(c)) to protease-resistant, beta-sheet rich, aggregates (PrP(sc)) is commonly accepted cause for prion diseases. On the other hand, several studies in recent years implicate soluble, protease-sensitive, oligomers of PrP(c) 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.

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