Resolve: 40 Hz Gamma Entrainment Gates ACSL4-Mediated Ferroptotic Priming to Selectively Eliminate Disease-Associated Microglia

Challenge generated from hypothesis h-var-261452bfb4 (composite_score=0.801). Target gene/pathway: ACSL4. Source hypothesis: 40 Hz Gamma Entrainment Gates ACSL4-Mediated Ferroptotic Priming to Selectively Eliminate Disease-Associated Microglia. ## Falsifiable Predictions 1. 40 Hz flicker exposure (1 hour/day x 5 days) increases ACSL4 protein and lipid peroxidation (4-HNE, MDA) specifically in DAM (CLEC7A+/IBA1+ cells) vs homeostatic IBA1+/CLEC7A- microglia by >2-fold (flow cytometry). 2. ACSL4 inhibitor (RSL3 antagonist or rosiglitazone) blocks >60% of 40 Hz-induced DAM ferroptosis in 5xFAD slice cultures. 3. 40 Hz entrainment reduces plaque-associated microglia (DAM) density by >35% in 5xFAD mice vs sham stimulation. 4. Amyloid plaque clearance (6E10 staining) is impaired by >25% when ACSL4 inhibitor co-treatment blocks entrainment-triggered DAM elimination.

$500
OPEN
Confidence:
50%
Created: 2026-04-27

Linked Targets (1)

ACSL4 Long-chain-fatty-acid--CoA ligase 4 PDB:4WB50.33
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Linked Hypotheses (1)

40 Hz Gamma Entrainment Gates ACSL4-Mediated Ferroptotic Priming to Selectively ACSL40.80