Cellular antioxidant and redox regulation systems

Cellular antioxidant and redox regulation systems represent a coordinated network of enzymes and molecules designed to maintain intracellular redox homeostasis and mitigate oxidative damage [1]. This system primarily includes the glutathione (GSH) and thioredoxin (Trx) pathways, alongside the master transcriptional regulator Nuclear factor erythroid 2-related factor 2 (Nrf2), which controls the expression of numerous cytoprotective genes [2][3]. These systems are critical for neutralizing reactive oxygen species (ROS) and reactive nitrogen species (RNS) generated during mitochondrial respiration and environmental exposure [4]. In therapeutic contexts, these systems are targeted in two opposing ways: activation to protect against neurodegeneration, inflammation, and aging, or inhibition to overcome chemoresistance in cancer cells that exploit these pathways for survival [5]. For example, Nrf2 activators like dimethyl fumarate are used in multiple sclerosis, while thioredoxin reductase inhibitors like auranofin are investigated for oncology [6]. However, modulating these systems is challenging due to the "antioxidant paradox," where excessive antioxidant activity may inadvertently support the survival of pre-malignant cells or disrupt essential redox signaling [7].

Other names

Redox homeostasis systemAntioxidant defense systemCellular redox bufferThiol-redox systemRedox regulation network

Modulation of the Nrf2-ARE signaling pathway, replenishment of thiol-based antioxidant pools (GSH/Trx), or direct scavenging of reactive oxygen species (ROS) [2][5][6].