NR AXQO
AU Kuczius,T.; Grassi,J.; Koch,R.; Karch,H.; Groschup,M.H.
TI Phenotypic Heterogeneity of Cellular Prion Proteins in Human, Sheep, Cattle and the Mouse
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Protein Misfolding P01.26
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Prion diseases are neurodegenerative disorders affecting both humans and animals. During pathogenesis the host encoded cellular prion protein (PrPc) is converted into its infectious isoform (PrPsc) which accumulates mainly in favoured brain regions. PrPsc is partial resistant to proteases, insoluble in detergent solutions and highly resistant to inactivation procedures. Many different PrPsc glycoform banding patterns have been identified; however, it is not known why and which PrPsc glycoforms selectively accumulate in favoured brain regions. Little attention has been given so far to the differentiation of PrPc; however, these proteins are the "substrates" for development of prion diseases. Thus it is conceivable that some PrPc subspecies and conformations which are differentially and posttranslationally modified may interact more or less efficiently with PrPsc, and different protein isoforms will be formed during conversion. With a set of antibodies we therefore typed the PrPc glycoform banding patterns derived from different brains and regions by densitometry. We found heterogeneous PrPc phenotypes. One pattern is characterized by high signal intensity of the di glycosylated isoform using antibodies binding to the N-terminal region whereas the other exhibits high intensity for proteins consisting of non glycosylated full length and glycosylated truncated PrPc isoforms when using antibodies recognizing the C-
terminal region. PrPc are modified by attachment of various N-linked glycans which may influence protein solubility. Different PrPc protein profiles derived from one sample were identified on the basis of solubility by differential centrifugation. Taken together, we found marked variations in the processing of PrP which may lead to interregional differences in the glycoform composition of PrPsc.
AD T. Kuczius, R. Koch, H. Karch, University Hospital Münster, Institute for Hygiene, Germany; J. Grassi, CEA, Service de Pharmacologie et d'Immunologie, CEA/Saclay, France; M.H. Groschup, Diseases, Institute for Novel and Emerging Infectious, Germany
SP englisch
PO Schottland