2010
DOI: 10.2478/s11535-009-0070-9
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In vitro synergistic anti-prion effect of cholesterol ester modulators in combination with chlorpromazine and quinacrine

Abstract: In vitro synergistic anti-prion effect of cholesterol ester modulators in combination with chlorpromazine and quinacrine * E-mail: pania@unica.it°These authors contributed equally to this work. Received 06 October 2009; Accepted 16 December 2009Abstract: Our studies on the role of cholesterol in prion infection/replication showed that brains and peripheral cells of sheep susceptible-to or suffering-from Scrapie were characterized by an altered cholesterol homeostasis, and that drugs affecting cholesterol ester… Show more

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Cited by 4 publications
(6 citation statements)
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“…These results are in agreement with our previous findings [17,18], as well as with those of a recent systems biology study showing that the SOAT1 gene, encoding for the enzyme (i.e. ACAT1) responsible for cholesterol esterification, is the first of all cholesterol-related genes to be up-regulated in the brain of scrapie-infected mice [25].…”
Section: Discussionsupporting
confidence: 93%
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“…These results are in agreement with our previous findings [17,18], as well as with those of a recent systems biology study showing that the SOAT1 gene, encoding for the enzyme (i.e. ACAT1) responsible for cholesterol esterification, is the first of all cholesterol-related genes to be up-regulated in the brain of scrapie-infected mice [25].…”
Section: Discussionsupporting
confidence: 93%
“…In the current study, qualitative and quantitative lipid analyses by HPLC-MS revealed multiple anomalies associated with prion infection both in ScN2a cell cultures and scrapie-affected C57Bl/6 mouse brains, mainly consisting in abnormal accumulation of CE. These results are in agreement with our previous findings [ 17 , 18 ], as well as with those of a recent systems biology study showing that the SOAT1 gene, encoding for the enzyme (i.e. ACAT1) responsible for cholesterol esterification, is the first of all cholesterol-related genes to be up-regulated in the brain of scrapie-infected mice [ 25 ].…”
Section: Discussionsupporting
confidence: 93%
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“…A significant amount of genetic, biochemical, and pharmacological data highlighted that modifications in cholesterol esterification and trafficking are associated with Aβ and PrPsc biogenesis (Puglielli et al, 2001; Hutter-Paier et al, 2004; Bhattacharyya and Kovacs, 2010; Huttunen et al, 2010; Pani et al, 2007a,b,c, 2011; Orrù et al, 2010a,b,c). Moreover, several studies in various cell and animal models of AD evidenced that, genetic or pharmacological inhibition of ACAT activity markedly suppresses Aβ generation.…”
Section: Ce and Neurodegenerationmentioning
confidence: 99%
“…In this context, our recent findings in sheep scrapie indicated that modifications of cholesterol metabolism, rather than being limited to the brain, appear to be a systemic trait since also ex vivo dermal fibroblasts and blood lymphocytes of sheep suffering-from or susceptible-to scrapie display similar alterations [12][13][14]. In addition, in prion/cell systems we found that persistent infection is associated to metabolic changes involving, besides cholesterol, all major classes of intracellular lipids, and that treatments with drug combinations triggering lipid homeostasis determine a synergic inhibition of prion generation [13,15,16]. In brains and skin fibroblasts from scrapie susceptible/infected sheep, the accumulation of cholesterol esters is accompanied by altered expression levels of enzymatic activities involved in cholesterol esterification (ACAT-1; up-regulated) and cholesterol trafficking (Cav-1; down-regulated), and by that of PrP C itself (up-regulated), Fig.…”
Section: Introductionmentioning
confidence: 99%