NR AOPZ
AU Barret,A.; Gallet,P.F.; Simoneau,S.; Forestier,L.; Jayat-Vignolles,C.; Larramendy,C.; Papy-Garcia,D.; Barritault,D.; Julien,R.; Deslys,J.P.
TI Glycogenome expression changes in prion infected cells and after treatment by heparan mimetics
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-100
PT Konferenz-Poster
AB
The glycogenome expression and function are still poorly understood in prion infections. However PrP, the prion protein, exhibits a complex glycosylation pattern and its profile is different depending on the infectious strain of prion. Moreover heparan sulfate, a major component of the extracellular matrix, which synthesis has been reported as modified in Alzheimer disease, interact with PrP and its cellular receptor. The role of these molecules could even be more prominent since we have demonstrated that a new class of heparan mimetics, initially developed for their effect on tissue regeneration, exhibited remarkable efficiency* to cure chronically scrapie infected cells (ScGT1). This cellular model, derived from murine hypothalamic neuronal cells, offers the advantage of a more stable infection than the classical ScN2a model and turned out to be more reliable to predict in vivo efficiency of new therapeutical approaches**.
In this cellular model, infected or not and treated or not by heparan mimetics, we have examined the glycosylation genes whose altered expression may be associated with prion protein misfolding and neurodegenerative disorders by DNA micro-array analysis. We have evidenced 4 genes for which the expression was modified in scrapie infected GT1 cells (1 was over-expressed while 3 others were under-expressed). This pattern was reversed by heparan mimetics treatment and these different results have been confirmed by real time RT-PCR. The respective roles of these deregulations in glycosaminoglycan synthesis will be discussed to analyse the role of sulfated glycans in prion infections.
* KT Adjou et al., J. Gen.Virol., 2003
** A.Barret et al., J. Virol., 2003
AD Agnès Barret, Steve Simoneau, Claire Larramendy, Jean-Philippe Deslys, Commissariat à l'Energie Atomique, DSV/DRM, Fontenay-aux-Roses, France; Paul-François Gallet, Lionel Forestier, Chantal Jayat-Vignolles, Raymond Julien, UMR 1061, Unité de Génétique Moléculaire Animale, INRA/Université de Limoges, France; Dulce Papy-Garcia, OTR3 Sarl,Créteil, France; Dulce Papy-Garcia, Denis Barritault, Laboratoire CRRET, CNRS FRE24-12, Université Paris XII-Val de Marne, France
SP englisch
PO Deutschland