Lipid peroxidation and oxidative stress pathways

Lipid peroxidation and oxidative stress pathways encompass the biochemical processes where reactive oxygen species (ROS) overwhelm cellular antioxidant defenses, leading to the oxidative degradation of lipids, particularly polyunsaturated fatty acids (Ayala et al., 2014, Oxidative Medicine and Cellular Longevity). This cascade results in the formation of reactive aldehydes like malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), which can further damage proteins and DNA (Tsikas, 2017, Journal of Chromatography B). Oxidative stress is a fundamental driver of cellular dysfunction and is linked to the pathogenesis of neurodegenerative diseases, cardiovascular disorders, and cancer (Pizzino et al., 2017, Oxidative Medicine and Cellular Longevity). A specific form of regulated cell death, ferroptosis, is defined by iron-dependent lipid peroxidation and is regulated by enzymes such as glutathione peroxidase 4 (GPX4) (Dixon et al., 2012, Cell). Pharmacological intervention in these pathways involves the use of antioxidants, such as Edaravone or N-acetylcysteine, which scavenge free radicals or replenish glutathione levels to restore redox homeostasis (Bhattacharyya et al., 2014, Physiological Reviews). Additionally, targeting the Nrf2 transcription factor is a major strategy to upregulate endogenous protective enzymes against oxidative damage (Kansanen et al., 2013, Redox Biology).

Other names

Oxidative stress responseLipid peroxidation cascadeRedox signaling pathwaysReactive oxygen species (ROS) pathwaysFerroptosis signaling pathway

Drugs targeting these pathways typically act as free radical scavengers, iron chelators, or activators of endogenous antioxidant systems such as the Nrf2-Keap1 signaling axis and glutathione peroxidase 4 (GPX4) activity to neutralize reactive oxygen species and prevent lipid membrane degradation.