RT Journal Article SR Electronic T1 The Selective Alzheimer's Disease Indicator-1 Gene (Seladin-1/DHCR24) Is a Liver X Receptor Target Gene JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 1716 OP 1721 DO 10.1124/mol.108.048538 VO 74 IS 6 A1 Yongjun Wang A1 Pamela M. Rogers A1 Keith R. Stayrook A1 Chen Su A1 Gabor Varga A1 Qi Shen A1 Sunil Nagpal A1 Thomas P. Burris YR 2008 UL http://molpharm.aspetjournals.org/content/74/6/1716.abstract AB The nuclear hormone receptors liver X receptor α (LXRα) and LXRβ function as physiological receptors for oxidized cholesterol metabolites (oxysterols) and regulate several aspects of cholesterol and lipid metabolism. Seladin-1 was originally identified as a gene whose expression was down-regulated in regions of the brain associated with Alzheimer's disease. Seladin-1 has been demonstrated to be neuroprotective and was later characterized as 3β-hydroxysterol-Δ24 reductase (DHCR24), a key enzyme in the cholesterologenic pathway. Seladin-1 has also been shown to regulate lipid raft formation. In a whole genome screen for direct LXRα target genes, we identified an LXRα occupancy site within the second intron of the Seladin-1/DHCR24 gene. We characterized a novel LXR response element within the second intron of this gene that is able to confer LXR-specific ligand responsiveness to reporter gene in both HepG2 and human embryonic kidney 293 cells. Furthermore, we found that Seladin-1/DHCR24 gene expression is significantly decreased in skin isolated from LXRβ-null mice. Our data suggest that Seladin-1/DHCR24 is an LXR target gene and that LXR may regulate lipid raft formation. The American Society for Pharmacology and Experimental Therapeutics