NR AXWL
AU Sissoeff,L.; Lamarrendy-Gozalo,C.; Maujeul,M.; Bonnet,C.; Riffet,C.; Papy-Garcia,D.; Barritault,D.; Deslys,J.P.
TI Differential Effect of Several Different Polyanionic Molecules on PrP Metabolism
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.118
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Several anti-prion drugs have a proven efficiency in vitro but have exhibited disappointing results in vivo. Among these compounds, sulfated polyanionic glycans have been especially well studied because they are structurally related to glycosaminoglycans (GAGs) synthetized by cells and appear to compete with them in prion replication (Caughey et al., 1993). Their main drawback (related to size and degree of sulfation) is an anticoagulant side effect.
We tested the two most efficient previously described molecules (pentosan polysulfate (PPS) and CR36, Larramendy-Golzalo et al. 2007) versus natural molecules of respectively similar molecular weights, i.e. enoxaparin (MW 4.500) and heparin (MW 15.000). We analysed the influence of these compounds on PrPc internalization and on PrPres decrease. The heaviest compounds (CR36 and heparin) were the most effective in curing cells. Moreover, we observed a correlation between PrPres decrease and the disappearance of PrPc from the cell surface. A similar subcellular relocalization of PrPc is seen in non infected cells. Three of these four molecules (CR36, heparin and PPS) induced an endocytosis of PrPc after treatment and a localization PrPc in rab6 positive compartments corresponding to Golgi network. However, only two of the molecules (PPS and heparin) induced a relocalization of a portion of PrPc with rab11 positive patterns corresponding to recycling endosomes. This could explain why PPS and CR36 act in a different way in vivo (Larramendy et al. 2007).
Synergystic effects differed for different combinations of these molecules. The elucidation of the mechanisms underlying the effect of anti-prion drugs is essential for the exploration of new therapeutical approaches.
Caughey et al., 1993; J Virol. 1993 Feb; 67(2):643-50. Larramendy-Gozalo et al., 2007; J Gen Virol. 2007 Mar; 88(3):1062-7.
AD L. Sissoeff, C. Lamarrendy-Gozalo, M. Maujeul, C. Bonnet, J.P. Deslys, CEA/DSV/IMETI/SEPIA, France; C. Riffet, D. Papy-Garcia, Laboratoire CRRET, CRNS FRE24-12, Université Paris XII-Val de Marne, France; D. Barritault, OTR3 sarl, France
SP englisch
PO Schottland
EA pdf-Datei und Poster (Postertitel: Early modifications of PrP metabolism after treatment with heparan molecules)