Cellular stress response and antioxidant pathways

The cellular stress response and antioxidant pathways comprise a sophisticated network of signaling cascades that enable cells to survive various physiological and environmental insults, such as oxidative stress, thermal shock, and chemical toxins (He et al., 2020, Signal Transduction and Targeted Therapy). A primary component is the Nrf2-KEAP1-ARE pathway, which serves as a master regulator of the antioxidant response by controlling the transcription of genes involved in detoxification and redox balance (Kansanen et al., 2013, Redox Biology). Additionally, the heat shock response (HSR) and the unfolded protein response (UPR) play critical roles in maintaining proteostasis by managing protein folding and degradation under stress. Dysregulation of these pathways is a hallmark of many chronic conditions, including neurodegenerative diseases like Parkinson's and Alzheimer's, where insufficient antioxidant defense leads to neuronal death, and cancer, where overactive stress responses can confer resistance to chemotherapy (Tonelli et al., 2018, Antioxidants & Redox Signaling). Pharmacological strategies often focus on Nrf2 activators to boost cellular resilience or inhibitors to sensitize tumor cells. However, because this term describes a broad biological process involving multiple distinct molecular entities rather than a single protein, it is classified as a pathway network rather than a discrete therapeutic target.

Other names

Oxidative stress responseAntioxidant defense systemCellular stress signalingRedox homeostasis pathways

Modulation of these pathways typically involves the activation of transcription factors like Nrf2 (Nuclear factor erythroid 2-related factor 2) which binds to Antioxidant Response Elements (ARE) to induce protective genes, or the induction of heat shock proteins (HSPs) to maintain proteostasis (Kansanen et al., 2013; Tonelli et al., 2018).