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Fig. 3 | Molecular Neurodegeneration

Fig. 3

From: Melatonin: a ferroptosis inhibitor with potential therapeutic efficacy for the post-COVID-19 trajectory of accelerated brain aging and neurodegeneration

Fig. 3

Mechanism of lipid peroxidation. Lipid peroxidation occurs in three steps: 1-initiation, 2-propagation, and 3-termination. 1- Initiation: the vicious cycle of lipid peroxidation starts with a radical attack (X) which reacts with polyunsaturated fatty acids (PUFA) in cell membrane phospholipids (PL) and removes their bis-allylic hydrogen, transforming PUFA into a lipid/ alkyl radical (PL-PUFA). 2- Propagation: Once a lipid radical is formed, a chain reaction of lipid radical formation continues. Molecular oxygen (O2) reacts with the formed PL-PUFA, producing a lipid peroxyl radical (PL-PUFAOO) which interacts with another membrane PL-PUFA, removes its bis-allylic hydrogen to form a lipid hydroperoxide radical (PL-PUFA-OOH) and another PL-PUFA that propagates the cycle. 2\- Amplification: iron feeds this chain reaction through a Fenton-like reaction. Ferrous iron (Fe+2) reacts with PL-PUFA-OOH, gets oxidized to Fe+3, and forms a hydroxide anion and a highly reactive alkoxyl (PL-PUFA-O) radical that causes an exponential increase in lipid radical formation. 3- Termination: the cycle can be ended either by the presence of an antioxidant that turns radicals into non-radicals or by the interaction of two radicals, forming O2 and a non-radical

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