ACSL4-Driven Ferroptotic Priming in Disease-Associated Microglia

h-seaad-v4-26ba859b

## 1. Molecular Mechanism and Rationale ACSL4 (acyl-CoA synthetase long-chain family member 4) catalyzes the esterification of arachidonic acid (AA, C20:4) and adrenic acid (AdA, C22:4) into membrane phospholipids, specifically phosphatidylethanolamines (PE-AA and PE-AdA). These polyunsaturated fatty acid (PUFA)-containing phospholipids serve as the primary substrates for iron-catalyzed lipid per

Elo ratings (across arenas)

Arena	Rating	RD	W-L-D	N
loop:loop-e96d7318f40f	1852	±219	4-0-0	4
alzheimers-demo	1809	±239	3-0-0	3
alzheimers	1757	±75	24-19-0	43
global	1712	±135	7-3-0	10
test-alzheimers	1662	±290	1-0-0	1

Ancestry (oldest → this)

(no parents — root hypothesis)

Descendants

mutate LPCAT3-Mediated Lands Cycle Remodeling as the Primary Ferroptotic Priming Engine

1246 (4 matches)

mutate ACSL4-Driven Ferroptotic Priming in Disease-Associated Oligodendrocytes Underlie

1252 (4 matches)

crossover 40 Hz Gamma Entrainment Gates ACSL4-Mediated Ferroptotic Priming to Selectively

1496 (23 matches)

mutate LPCAT3-Mediated Lands Cycle Amplification of Ferroptotic Substrate Pools in Dise

1287 (4 matches)

mutate ACSL4-Ferroptotic Priming in Stressed Oligodendrocytes Drives White Matter Degen

1313 (8 matches)

mutate LPCAT3-Mediated Lands Cycle Amplification of Ferroptotic Vulnerability in Diseas

1194 (10 matches)

mutate ALOX15-Driven Enzymatic Ferroptosis in AD Oligodendrocytes via PUFA-PE Peroxidat

1265 (10 matches)