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Lipids are most abundant in the human brain among all tissues except adipose tissue ( Enzymes like acyl-CoA synthetase long-chain family member 4 (ACSL4) and lysophosphatidylcholine acyltransferase 3 (LPCAT3) are central to incorporating PUFAs into membranes, sensitizing cells to ferroptosis ( As non-heme iron-containing dioxygenases, lipoxygenases (LOXs) directly catalyze the peroxidation of PUFAs, both free and esterified in phospholipids ( PTC-041, a selective 15-LOX inhibitor, blocks lipid peroxidation and the ferroptosis pathway by inhibiting enzyme activity in its reduced hydroquinone form