Plasma cholesterol level determines in vivo prion propagation.
Fiche publication
Date publication
août 2017
Journal
Journal of lipid research
Auteurs
Membres identifiés du Cancéropôle Est :
Dr LAGROST Laurent
Tous les auteurs :
Perrier V, Imberdis T, Lafon PA, Cefis M, Wang Y, Huetter E, Arnaud JD, Alvarez-Martinez T, Le Guern N, Maquart G, Lagrost L, Desrumaux C
Lien Pubmed
Résumé
Transmissible spongiform encephalopathies (TSE) are fatal neurodegenerative diseases with an urgent need for therapeutic and prophylactic strategies. At the time when the blood-mediated transmission of prions was demonstrated, in vitro studies indicated a high binding affinity of the scrapie prion protein (PrPSc) with apolipoprotein B-containing lipoproteins, i.e. the main carriers of cholesterol in human blood. The aim of the present study was to explore the relationship between circulating cholesterol-containing lipoproteins and the pathogenicity of prions in vivo. We showed that in mice with a genetically-engineered deficiency for the plasma lipid transporter phospholipid transfer protein (PLTP), abnormally low circulating cholesterol concentrations were associated with a significant prolongation of survival time after intraperitoneal inoculation of the 22L prion strain. Moreover, when circulating cholesterol levels rose after feeding PLTP-deficient mice a lipid-enriched diet, a significant reduction in survival time of mice together with a marked increase in the accumulation rate of PrPSc deposits in their brain were observed. Our results suggest that the circulating cholesterol level is a determinant of prion propagation in vivo, and that cholesterol lowering strategies might be a successful therapeutic approach for patients suffering from prion diseases.
Mots clés
animal models, brain, encephalopathy, lipid transfer proteins, lipoproteins, neurodegenerative diseases, neurons
Référence
J. Lipid Res.. 2017 Aug;: