Resolve: Selective LXRβ agonists restore ABCA1/ABCG1 expression and APOE lipidation in APOE4 astrocytes

Falsifiable prediction from high-scoring hypothesis (score=0.728, gene=NR1H2 (LXRβ), ABCA1, ABCG1). Hypothesis: Can selective LXRβ agonism restore cholesterol efflux in APOE4 astrocytes by upregulating ABCA1/ABCG1, normalizing APOE lipidation, and reducing amyloid-driven neurotoxicity? Success criteria: 1. LXRβ-selective agonist (e.g., BMS-986192) increases ABCA1/ABCG1 mRNA >2-fold in APOE4 iPSC-astrocytes vs vehicle. 2. APOE4 lipidation state (HDL-sized particles) improves by >35% after 48h LXRβ agonist treatment. 3. Conditioned media from LXRβ-treated APOE4 astrocytes reduces amyloid-beta toxicity in neuronal co-culture by >30% vs untreated. 4. In vivo: 5xFAD/APOE4 KI mice show >25% reduction in cortical plaque load after 12-week LXRβ agonist treatment.

$750

OPEN

Confidence:

70%

Created: 2026-04-28

Linked Targets (2)

APOE Apolipoprotein E PDB:3R4L0.62

🧬 View 3D Structure — PDB 3R4L click to expand

ABCA1 ATP-binding cassette transporter A1 PDB:7QS70.56

🧬 View 3D Structure — PDB 7QS7 click to expand

Detected Targets:

ABCA1 APOE

3D Protein Structure

▶ View 3D structure: ABCA1 — PDB 7TBJ

Experimental structure from RCSB PDB | Powered by Mol* | Rotate: click+drag | Zoom: scroll

Landscape analysis not yet run for this challenge. Run the landscape analyzer to get competitive intelligence.

Linked Hypotheses (1)

Selective LXRβ agonists restore ABCA1/ABCG1 expression and APOE lipidation in AP NR1H2 (LXRβ), ABCA1, ABCG10.76