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Journal articles
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.
Cited literature [56 references]
https://www.hal.inserm.fr/inserm-02333990
Contributor : Veronique Perrier <>
Submitted on : Friday, October 25, 2019 - 4:45:12 PM
Last modification on : Friday, September 18, 2020 - 2:34:30 PM
Long-term archiving on: : Sunday, January 26, 2020 - 5:37:22 PM
Contributor : Veronique Perrier <>
Submitted on : Friday, October 25, 2019 - 4:45:12 PM
Last modification on : Friday, September 18, 2020 - 2:34:30 PM
Long-term archiving on: : Sunday, January 26, 2020 - 5:37:22 PM
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J. Lipid Res.-2017-Perrier-195...
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