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Excel · study · 2026

Ciclosonide reduces lipid droplet burden in APOE4 astrocytes

Listed in NCBI GEO

Prior studies have shown that ApoE ε4 astrocytes display a higher LD count than ApoE ε3 astrocytes.

Description

We examined the effects of pharmacological agents on lipid droplets (LDs) in apolipoprotein E (ApoE) ε3 and ApoE ε4 astrocytes. We hypothesized that drugs reducing LDs in ApoE ε4 astrocytes could reveal mechanisms of LD formation and inform potential treatments for AD.

A screen of 2,321 FDA-approved drugs was conducted to identify candidates for investigating LD differences between ApoE ε3 and ApoE ε4 astrocytes. Both ApoE ε3 and ApoE ε4 astrocytes produced LDs detectable with BODIPY staining. PLIN2 co-staining ensured LD specificity.

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A drug screen and validation workflow identified three compounds, ciclosonide, VX745, and ipragliflozine, as reducing LDs in ApoE ε4 astrocytes specifically. Ciclesonide, a glucocorticoid with a known mechanism of action, showed dose-dependent effects on LD reduction (0.05, 0.5, and 5 mM). Transcriptomic analysis of ciclesonide-treated astrocytes revealed significant changes in extracellular matrix organization.

These findings enhance understanding of LD formation and isoform-specific differences in astrocytes. Given the role of LDs in AD, these insights may contribute to understanding AD pathogenesis and identifying therapeutic strategies.

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Life Sciences
Provenance · 1 source records, 7 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE34435114 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[organism].NCBITaxon:10090source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title