Pro-survival and Antioxidant Pathways

Pro-survival and Antioxidant Pathways refer to a complex network of intracellular signaling cascades and transcriptional programs, such as the Nrf2-KEAP1-ARE axis and the PI3K/Akt pathway, that protect cells from oxidative damage and promote longevity (Tonelli et al., 2018, Antioxidants & Redox Signaling). The Nrf2 pathway serves as a primary sensor for electrophilic and oxidative stress, triggering the expression of numerous cytoprotective enzymes like heme oxygenase-1 and glutathione S-transferases (Manning & Toker, 2017, Cell). Simultaneously, pro-survival kinases like Akt integrate extracellular growth signals to inhibit pro-apoptotic proteins and maintain cellular viability under adverse conditions. In therapeutic contexts, these pathways are often targeted for activation to treat neurodegenerative and inflammatory diseases, such as multiple sclerosis and Friedreich's ataxia, where oxidative stress is a major driver of pathology (FDA, 2013, Tecfidera Label). Conversely, in oncology, these pathways are frequently hijacked by malignant cells to survive harsh microenvironments and resist chemotherapy, making them targets for inhibition to restore treatment sensitivity. Because this term describes a broad biological category rather than a single molecular entity, it is generally considered a pathway network rather than a specific therapeutic target.

Other names

Antioxidant response element (ARE) pathwayCytoprotective pathwaysNrf2-KEAP1 signaling pathwayCell survival signalingRedox homeostatic pathways

Activation of the Nrf2-KEAP1-ARE axis to induce cytoprotective gene expression; modulation of PI3K/Akt/mTOR signaling to regulate cell survival and apoptosis.