Résumé
La protéine du prion (PrP) est une glycoprotéine ancrée par un glycosyl-phosphatidylinositol à la membrane, exprimée de manière constitutive dans la plupart des tissus et plus particulièrement au niveau neuronal. Sa fonction normale reste incertaine mais pourrait concerner le métabolisme des ions métalliques, la défense contre le stress oxydant ou encore les phénomènes de reconnaissance intercellulaires. La PrP joue un rôle majeur dans le déclenchement et la transmission des encephalopathies spongiformes subaiguës transmissibles, ou maladies à prions. L’hypothèse étiologique actuelle suggère que cette protéine, dans sa forme pathologique, représenterait l’agent infectieux. La PrP est en effet l’objet de modifications conformationelles très particulières au cours de la maladie. Ces dernières pourraient expliquer le caractère transmissible de ces affections ainsi que les phénomènes de neurodégénérescence observés.
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 have the property of being 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 has a 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 by a glycosyl-phosphatidylinositol anchor which would be 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. This is particularly relevant, knowing the possible role of the molecule in signal transduction, resistance to oxidative stress and neuronal survival. In conclusion, it appears that the understanding of the biology of PrP is essential for the understanding of the physiological function of the protein as well as for its pathological conversion considering that trafficking of this molecule governs generation of PrPSc.