1 4 - hydroxy - 2 - nonenal : a critical target in oxidative stress ? 1

20 In this perspective, we summarize and discuss critical advancements in the study of 421 hydroxy-2-nonenal (4-HNE) as it relates to diseases and clinical complications either caused or 22 exacerbated by oxidative stress. Since its identification in 1980, 4-HNE has been extensively 23 studied with an emphasis on its formation, its role in pathology, and its targets. As a reactive 24 aldehyde, and a product of lipid peroxidation, studies corroborate its ability to disrupt signal 25 transduction and protein activity, as well as induce inflammation and trigger cellular apoptosis in 26 conditions of oxidative stress. Notably, we discuss the role of natural enzymes involved in the 27 regulation of 4-HNE, and how they can be applied to its detoxification in various physiological 28