NR AWNV
AU Sissoeff,L.; Lamarrendy-Gozalo,C.; Mouthon,F.; Bellanger,L.; Mathieu,E.; Antonangeli,L.; Riffet,C.; Papy-Garcia,D.; Barritault,D.; Quemeneur,E.; Deslys,J.P.
TI Modifications of PrP metabolism in vitro after pentosan polysulfate treatment versus a new heparan mimetic
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions THE-17
PT Konferenz-Poster
AB Numerous compounds have already been evaluated in vitro for therapeutic purposes in prion diseases, with disappointing results in vivo. Sulfated polyanions, including polysulfate (PPS) and heparan mimetics, number among the more effective tested drugs. In this study, we focused precisely on the PrP metabolism after short treatments and on the anti-prion mechanism of a new Heparan mimetic (CR36) versus PPS. CR36 was much more efficient than PPS to reduce PrPres accumulation in the chronically infected Sc GT1 cell line with a long lasting anti-prion activity. As assessed by FACS analysis, both compounds reduced PrP expression at the cell surface in several cell lines, with no change in Prnp gene expression. This effect appeared to be specific of PrP-GPI and endogenous heparan sulfate proteoglycans were necessary for the PPS and CR36 effect. By using a strategy of complementation of PrP deficient cell with engineered PrP-GPI, we observed a extremely fast endocytosis post PrPcGPI incorporation into the plasma membrane for both compounds with moderate kinetic variations between CR36 and PPS. After cycloheximide pre-treatment of murine PrPc-GPI overexpressing CHO cells, an increase of the kinetic of PrP endocytosis was observed with CR36 versus PPS treatment. Immunocytochemistry experiments confirmed the decrease of PrP cell surface expression but also showed a different surface localization pattern of PrP after treatment with CR36 versus PPS. Thus, these two sulfated polyanions seem to decrease the PrPres precursor at the cell surface by different molecular mechanisms which need further investigations which could lead to original therapeutic approaches.
AD L.Sissoëff, C. Lamarrendy-Gozalo, F. Mouthon, E. Mathieu, L. Antonangeli, J.-P. Deslys: CEA/DSV/DRM/GIDTIP, 18 route du Panorama, 92265 Fontenay-aux-Roses, France; L. Bellanger, E. Quemeneur: CEA/DSV/DIEP/SBTN, BP 17171 30207 Bagnols-sur-Cèze, France; C. Riffet, D. Papy-Garcia: Laboratoire CRRET, CRNS FRE24-12, Université Paris XII-Val de Marne, Avenue du Général de Gaulle, 94010, Créteil, France; D. Barritault: OTR3 sarl, 4 rue Française, 75001 Paris, France
SP englisch
PO Italien