biostudies-literatureFan JAlzheimer's Drug Discovery FoundationCanadian Institutes of Health Researche0162384https://www.ebi.ac.uk/biostudies/studies/S-EPMC5012716biostudies-literatureUnknown11(9)The apolipoprotein E (APOE) gene is the most highly associated susceptibility locus for late onset Alzheimer's Disease (AD), and augmenting the beneficial physiological functions of apoE is a proposed therapeutic strategy. In a high throughput phenotypic screen for small molecules that enhance apoE secretion from human CCF-STTG1 astrocytoma cells, we show the chrysanthemic ester 82879 robustly increases expressed apoE up to 9.4-fold and secreted apoE up to 6-fold and is associated with increased total cholesterol in conditioned media. Compound 82879 is unique as structural analogues, including pyrethroid esters, show no effect on apoE expression or secretion. 82879 also stimulates liver x receptor (LXR) target genes including ATP binding cassette A1 (ABCA1), LXRα and inducible degrader of PloS oneIdentification of a Chrysanthemic Ester as an Apolipoprotein E Inducer in Astrocytes.PMC5012716209102.01106706Wellington CLFan JZareyan SZhao WKulic IIsman MBPfeifer TAVan den Hoven BShimizu YTak JHDuggan MEWood MWfalseIdentification of a Chrysanthemic Ester as an Apolipoprotein E Inducer in Astrocytes.The apolipoprotein E (APOE) gene is the most highly associated susceptibility locus for late onset Alzheimer's Disease (AD), and augmenting the beneficial physiological functions of apoE is a proposed therapeutic strategy. In a high throughput phenotypic screen for small molecules that enhance apoE secretion from human CCF-STTG1 astrocytoma cells, we show the chrysanthemic ester 82879 robustly increases expressed apoE up to 9.4-fold and secreted apoE up to 6-fold and is associated with increased total cholesterol in conditioned media. Compound 82879 is unique as structural analogues, including pyrethroid esters, show no effect on apoE expression or secretion. 82879 also stimulates liver x receptor (LXR) target genes including ATP binding cassette A1 (ABCA1), LXRα and inducible degrader of 2016-01-01T00:00:00Z20162026-04-08T16:15:42.68Z2019-03-26T22:52:41ZS-EPMC50127162759878210.1371/journal.pone.0162384