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Due to the existence of the conjugated system of C = C bonds and carbonyl groups, 4-HNE can provide partial positive charge to the carbon at position three and become efficient electrophiles, allowing it to react with essential biological molecules, including proteins and DNA (107109)

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In addition, previous studies have shown that mutations in the LCD of hnRNP A1 and A2 cause ALS and multisystem proteinopathy 77