Le rôle de la protéine du prion dans les encéphalopathies spongiformes transmissibles humaines.

Abstract

Les encéphalopathies spongiformes transmissibles forment un groupe très particulier d’affections neurodégénératives, d’origine à la fois infectieuse et génétique. L’hypothèse en faveur actuellement donne à une protéine, appelée la protéine du prion (PrP), un rôle central dans l’étiologie de ces affections. Qu’une protéine s’avère être elle-même un agent infectieux va à l’encontre des notions établies. Des travaux récents confortent pourtant cette hypothèse et suggèrent que les mécanismes impliqués dans la pathogénie pourraient dépasser le cadre des seules encéphalopathies spongiformes.

The spongiform encephalopathies are a group of fatal neurodegenerative diseases that includes Creutzfeldt-Jakob disease, kuru, Gerstmann-Straussler syndrome, and fatal familial insomnia in human beings. Also called prion diseases, these disorders are unique in being both infectious and genetic in origin. Mutations in the human gene that encodes the prion protein (PrP) are strongly linked to inherited forms of the disease. The agent responsible for infectious forms of the disease is thought to be a protein called PrP(Sc). PrP(Sc) corresponds to an altered form of the normal PrP(C). Several pieces of evidence indicate that PrP(Sc) and PrP(C) do not differ in their primary amino acid sequence, but rather in their conformations. Prion 'replication' is believed to occur when PrP(Sc) in the infecting inoculum interacts specifically with host PrP(C), catalyzing its conversion into PrP(Sc). Recent in vitro studies as well as the use of transgenic animals have given new insights into the comprehension of the mechanisms of these diseases. The conversion of PrP(C) into PrP(Sc) is now considered as the central event in the transmission as well as in the pathogenic process of prion diseases.