| First Author | Perrier V | Year | 2017 |
| Journal | J Lipid Res | Volume | 58 |
| Issue | 10 | Pages | 1950-1961 |
| PubMed ID | 28765208 | Mgi Jnum | J:250551 |
| Mgi Id | MGI:5916652 | Doi | 10.1194/jlr.M073718 |
| Citation | Perrier V, et al. (2017) Plasma cholesterol level determines in vivo prion propagation. J Lipid Res 58(10):1950-1961 |
| abstractText | 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. |
