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Plasma cholesterol level determines in vivo prion propagation

Abstract : Transmissible spongiform encephalopathies 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 apoB-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.Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.
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Contributor : Véronique Perrier Connect in order to contact the contributor
Submitted on : Friday, October 25, 2019 - 4:45:12 PM
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J. Lipid Res.-2017-Perrier-195...
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Véronique Perrier, Thibaud Imberdis, Pierre-André Lafon, Marina Cefis, yunyun Wang, et al.. Plasma cholesterol level determines in vivo prion propagation. Journal of Lipid Research, American Society for Biochemistry and Molecular Biology, 2017, 58 (10), pp.1950-1961. ⟨10.1194/jlr.M073718⟩. ⟨inserm-02333990⟩



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