Fonctions de la protéine prion PrPc

Abstract

Les maladies à prion (scrapie du mouton, maladie de la vache folle, maladie de Creutzfeldt- Jakob chez l’homme) impliquent les deux isoformes, normale PrPc et pathologique ou scrapie PrPsc, de la protéine prion. La protéine PrPc est fortement exprimée dans le système nerveux central (neurones, cellules gliales) mais est aussi présente dans les cellules du système immunitaire, et les cellules épithéliales et endothéliales. Des études récentes permettent de classer les fonctions de la PrPc en deux grands domaines : (1) la survie cellulaire et (2) l’adhérence cellulaire, celle-ci étant liée à différentes fonctions selon le type cellulaire (neuritogenèse, intégrité des barrières épithéliale et endothéliale, migration transendothéliale de monocytes, activation de lymphocytes T). Ces observations suggèrent des fonctions de la PrPc importantes notamment en situations de stress cellulaire inflammatoire et d’infection.

It is now well established that both normal and pathological (or scrapie) isoforms of prion protein, PrPc and PrPsc respectively, are involved in the development and progression of various forms of neurodegenerative diseases, including scrapie in sheep, bovine spongiform encephalopathy (or « mad cow disease ») and Creutzfeldt-Jakob disease in human, collectively known as prion diseases. The protein PrPc is highly expressed in the central nervous system in neurons and glial cells, and also present in non-brain cells, such as immune cells or epithelial and endothelial cells. Identification of the physiological functions of PrPc in these different cell types thus appears crucial for understanding the progression of prion diseases. Recent studies highlighted several major roles for PrPc that may be considered in two major domains : (1) cell survival (protection against oxidative stress and apoptosis) and (2) cell adhesion. In association with cell adhesion, distinct functions of PrPc were observed, depending on cell types : neuronal differentiation, epithelial and endothelial barrier integrity, transendothelial migration of monocytes, T cell activation. These observations suggest that PrPc functions may be particularly relevant to cellular stress, as well as inflammatory or infectious situations.