Résumé
Transmissible spongiform encephalopathies form a group of fatal neurodegenerative disorders represented principally by Creutzfeldt-jakob disease in humans, and by scrapie and bovine spongiform encephalopathy in animals. Also called prion diseases, these disorders are infectious, sporadic, or genetic in origin. Although the nature of the responsible agent of these diseases is uncertain, it is clear that a protein called PrPSc plays Q central role in their pathology. PrPSc is a conformational variant of a normal protein called PrPC. PrPC is a glycoprotein expressed by most tissues and is attached on the cell membrane through a glycosyl-phosphatidylinositol anchor, which is consistent with roles in cell adhesion, ligand uptake, or transmembrane signaling. NMR studies revealed that the protein has a globular domain and a long amino-terminal tail that contains repeated octapeptide domains, which bind metal ions with high affinities. PrPC is localized on the cell membrane in detergent resistant microdomains and may be part of functional complexes with other molecules such as N-CAM, Laminin or kinases. This is particularly relevant in view of the possible role of the molecule in signal transduction, resistance to oxidative stress and neuronal survival, The description both in vitro and in vivo, of a transmembrane form of PrP that can accumulate in the endoplasmic reticulum has attracted a lot of attention. The role of such isoforms in neurodegeneration, as well as the presence of PrP into the cytoplasm and in the nucleus where it may interact with nucleic acids are still debated. In conclusion, it appeared that the understanding of the PrP biology is essential to the understanding of the physiological function of this protein as well as for its pathological conversion since its trafficking governs the generation of PrPSc.