Details

Autor(en) / Beteiligte

• Pan, Tao
• Li, Ruliang
• Kang, Shin‐Chung
• Pastore, Manuela
• Wong, Boon‐Seng
• Ironside, James
• Gambetti, Pierluigi
• Sy, Man‐Sun

Titel

Biochemical fingerprints of prion diseases: scrapie prion protein in human prion diseases that share prion genotype and type

Ist Teil von

• Journal of neurochemistry, 2005-01, Vol.92 (1), p.132-142

Ort / Verlag

Oxford, UK: Blackwell Science Ltd

Erscheinungsjahr

2005

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• The phenotype of human prion diseases is influenced by the prion protein (PrP) genotype as determined by the methionine (M)/valine (V) polymorphism at codon 129, the scrapie PrP (PrPSc) type and the etiology. To gain further insight into the mechanisms of phenotype determination, we compared two‐dimensional immunoblot profiles of detergent insoluble and proteinase K‐resistant PrP species in a type of sporadic Creutzfeldt‐Jakob disease (sCJDMM2), variant CJD (vCJD) and sporadic fatal insomnia (sFI). Full‐length and truncated PrP forms present in the insoluble fractions were also separately analyzed. These three diseases were selected because they have the same M/M PrP genotype at codon 129 and the same type 2 PrPSc, but different etiologies, also sCJDMM2 and sFI are sporadic, whereas vCJD is acquired by infection. We observed minor differences in the PrP detergent‐insoluble fractions between sCJDMM2 and vCJD, although both differ in the corresponding fractions from sFI. We detected more substantial heterogeneity between sCJDMM2 and vCJD in the two‐dimensional blots of the proteinase K‐resistant PrP fraction suggesting that different PrP species are selected for conversion to proteinase K‐resistant PrP in sCJDMM2 and vCJD. These differences are mostly, but not exclusively, due to variations in the type of the N‐linked glycans. We also show that the over‐representation of the highly glycosylated forms distinctive of the proteinase K‐resistant PrPSc of vCJD in one‐dimensional blots is due to differences in both the amount and the natures of the glycans. Overall, these findings underline the complexity of phenotypic determination in human prion diseases.