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- W2000673403 abstract "The liver X receptors (LXRα and LXRβ) are transcription factors that control the expression of genes primarily involved in cholesterol metabolism. In the brain, in addition to normal neuronal function, cholesterol metabolism is important for APP proteolytic cleavage, secretase activities, Aβ aggregation and clearance. Particularly significant in this respect is LXR mediated transcriptional control of APOE, which is the only proven risk factor for late onset Alzheimer’s disease. Using a transactivation reporter assay for screening pharmacologically active compounds and off patent drugs we identified the proton pump inhibitor Lansoprazole as an LXR agonist. In secondary screens and counter-screening assays, it was confirmed that Lansoprazole directly activates LXR, increases the expression of LXR target genes in brain-derived human cell lines, and increases Abca1 and Apo-E protein levels in primary astrocytes derived from wild type but not LXRα/β double knockout mice. Other PPIs activate LXR as well, but the efficiency of activation depends on their structural similarities to Lansoprazole. The identification of a widely used drug with LXR agonist-like activity opens the possibility for systematic preclinical testing in at least two diseases—Alzheimer’s disease and atherosclerosis." @default.
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- W2000673403 date "2010-05-01" @default.
- W2000673403 modified "2023-10-16" @default.
- W2000673403 title "Proton pump inhibitor Lansoprazole is a nuclear liver X receptor agonist" @default.
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- W2000673403 doi "https://doi.org/10.1016/j.bcp.2009.12.018" @default.
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