NR AOSA
AU Dumpitak,C.; Leffers,K.W.; Birkmann,E.; Riesner,D.
TI Influences of polysaccharides and age-related protein modifications onto prion-protein-aggregation
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-33
PT Konferenz-Poster
AB
To understand the pathological properties of prions in more detail, knowledge about the influence of secondary components onto prion-formation is essential. This is especially important since in-vitro reconstitution of infectivity could not be shown by now. After intense PK-digestion a polysaccharide scaffold (prionscaffold) was found in prion rods (PrP 27-30) as a secondary component, amounting 5-15% of PrP 27-30. It consisted of predominantly alpha-1,4-linked glucose with few alpha-1,4,6-branches, showing high similarity to aged glycogen. The influence of such a polysaccharide onto the conformational transition of PrP was studied, applying an in vitro transition system, in which PrP was kept soluble at low concentrations of sodiumdodecylsulfate (SDS) and undergoes conformational transition with aggregation after dilution of SDS. When glycogen was used as a model for the prionscaffold, aggregation of PrP was highly accelerated and led to a higher amount of PrP-aggregates, which had a smaller size compared to aggregation without glycogen. The results clearly show that glycogen can act as a seed for PrP-aggregation.
Furthermore the questions were addressed if ageing-related advanced glycation endproducts (AGEs) could participate in prion pathogenesis. AGE-analysis showed that in comparison to non-infectious and cellular PrP-species, PrP 27-30 had a lesser degree of AGE-modifications, suggesting that the conformational switch from PrPc to PrPsc should take place early after PrP-translation. In vitro AGEing of rec PrP lead to aggregation, thus suggesting a potential fuction as seed for PrP-aggregation as well.
AD C. Dumpitak, K.-W. Leffers, E. Birkmann, D. Riesner, Institut für Physikalische Biologie and Biologisch-Medizinisches-Forschungszentrum, Heinrich-Heine-Universität Düsseldorf, D-40225 Düsseldorf, Germany
SP englisch
PO Deutschland