NR ATQJ
AU Lenuzza,N.; Charveriat,M.; Buon,J.G.; Picoli,C.; Freire,S.; Correia,E.; Benhamida,S.; Iris,F.; Deslys,J.P.; Mouthon,F.
TI New insight in prion pathogenesis : from theoretical model of neuropathogenesis to experimental evaluations
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Pathogenesis PATH-46
PT Konferenz-Poster
AB
Neuropathogenesis of Prion diseases involve, on the one hand, the prion protein itself and, on the other hand, neurons, astrocytes and microglial cells, by molecular mechanisms remaining unknown.
An original approach has developed a theoretical model of Prion neuropathogenesis. Integrative analytical procedures based upon the main public databases allowed to define a complex network of large biological processes using molecular partner interactions and signalization pathways. Specific data about Prion diseases have been tested in this network for the construction of different hypothesis. Our theoretical model described a tripartite implication of neurones, astrocytes and microglial cells with successive molecular alterations leading to vicious circles which corrupt the physiological stability.
To evaluate the neuropathological mechanisms predicted by this theoretical model, we focused our experimental study on three original targets neither described in Prion fields nor in neurodegenerative diseases. We used two complementary approaches to evaluate the relevance of these targets, based on the study of gene expression modifications in vivo and in vitro and the other one based on the immunohistochemical localization in vivo.
Interestingly, two of the studied targets are modified in infected GT1-7 cells and in the mice infected versus non infected controls. These modifications as predicted by the model, seem to desorganize the cytoskeleton components associated to the membrane, early in the neurons and later in the activated astrocytes.
Thus, our results show for the first time that a theoretical model can predict new pathways and corresponding targets involved in neuropathogenesis mechanism underlying prions diseases.
AD N.Lenuzza, M.Charveriat, J.G.Buon, C.Picoli, S.Freire, E.Correia, J.P.Deslys, F.Mouthon, CEA/DSV/DRM/GIDTIP, Route du panorama, 92265 Fontenay-aux-Roses, France; S.Benhamida, Pole Santé-Biotechnologies, Ecole Centrale Paris, Chatenay-Malabry, France; F.Iris, Bio-Modeling Systems, France
SP englisch
PO Deutschland