Antioxidant defense proteins

Antioxidant defense proteins comprise a diverse group of enzymes and non-enzymatic proteins dedicated to maintaining cellular redox homeostasis by neutralizing reactive oxygen species (ROS) and reactive nitrogen species (RNS) [1]. Key members include superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and the thioredoxin system, which work coordinately to prevent oxidative damage to DNA, proteins, and lipids [2]. Many of these proteins are transcriptionally regulated by the Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, which acts as a master regulator of the endogenous antioxidant response [3]. Dysregulation of these proteins is implicated in a wide range of diseases, including neurodegenerative disorders, cardiovascular diseases, and chronic inflammatory conditions [4]. In oncology, antioxidant defense proteins play a dual role: they protect normal cells from malignant transformation but can also be hijacked by tumor cells to survive metabolic stress and resist chemotherapy [5]. Therapeutic interventions often focus on inducing these endogenous defenses using Nrf2 activators like bardoxolone methyl or employing small-molecule mimetics of enzymes like SOD [6]. However, excessive suppression of ROS can lead to "reductive stress," potentially interfering with essential signaling pathways required for normal physiological functions [7]. [1] Halliwell B, Gutteridge JM. Free Radicals in Biology and Medicine. Oxford University Press; 2015. [2] Sies H, et al. Nat Rev Mol Cell Biol. 2017;18(6):355-365. [3] He F, et al. QJM. 2020;113(11):771-779. [4] Forman HJ, Zhang H. Nat Rev Drug Discov. 2021;20(9):689-709. [5] Harris IS, DeNicola GM. Trends Cancer. 2020;6(8):678-687. [6] Kensler TW, et al. Top Curr Chem. 2013;329:163-177. [7] Xiao W, Loscalzo J. Antioxid Redox Signal. 2020;32(18):1330-1347.

Other names

Antioxidant enzymesROS scavenging proteinsRedox-regulating proteinsEndogenous antioxidants

Induction of endogenous antioxidant gene expression via the Nrf2-KEAP1 pathway or direct catalytic scavenging of reactive oxygen species.