ACSL4-Driven Ferroptosis in Disease-Associated Microglia: Therapeutic Opportunity in AD

Single-cell transcriptomic analyses (SEA-AD, Allen Brain Cell Atlas) identify ACSL4 upregulation in specific microglial subtypes near amyloid plaques. ACSL4 promotes arachidonic acid incorporation into phospholipids, sensitizing cells to ferroptosis. Whether ferroptotic flux drives AD pathology or represents a protective mechanism remains unresolved.

$2.6M

OPEN

Confidence:

75%

Created: 2026-04-17

Scoring Dimensions

Gap Importance0.88

Therapeutic Potential0.83

Investment Level0.00

Urgency0.80

Landscape Score0.67

Composite Score 0.800

Linked Targets (2)

GPX4 Glutathione peroxidase 4 PDB:2OBI0.57

🧬 View 3D Structure — PDB 2OBI click to expand

ACSL4 Long-chain-fatty-acid--CoA ligase 4 PDB:4WB50.33

🧬 View 3D Structure — PDB 4WB5 click to expand

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Linked Hypotheses (1)

ACSL4-Driven Ferroptotic Priming in Disease-Associated Microglia ACSL40.85