Redox regulatory system (RRS) (RRS)

The redox regulatory system is a complex network of enzymes, antioxidants, and signaling molecules dedicated to maintaining cellular redox homeostasis by balancing the production and elimination of reactive oxygen species (ROS) and reactive nitrogen species (RNS) [1]. Key components include the glutathione (GSH) system, the thioredoxin (Trx) system, and various antioxidant enzymes such as superoxide dismutase (SOD) and catalase [2]. This system plays a critical role in protecting cells from oxidative stress, which can damage DNA, proteins, and lipids, leading to various pathologies [3]. In many diseases, such as cancer and neurodegeneration, the redox regulatory system is often hijacked or impaired; for instance, cancer cells frequently upregulate antioxidant pathways to survive high ROS levels and resist chemotherapy [4]. Pharmacological modulation of this system involves either activating cytoprotective pathways (e.g., Nrf2 activators) or inhibiting specific redox enzymes to induce ferroptosis or apoptosis in diseased cells [5].

Other names

Redox homeostasis systemAntioxidant defense systemThiol-redox systemCellular redox environment

The mechanism of action for drugs targeting the redox regulatory system involves the modulation of key enzymatic pathways and transcription factors to restore or disrupt redox balance. Nrf2 activators, such as Bardoxolone methyl, induce the expression of antioxidant response element (ARE)-driven genes to enhance cellular defense [6]. Conversely, inhibitors like Auranofin target thioredoxin reductase to increase oxidative stress and induce apoptosis in cancer cells [7]. Other agents, like N-acetylcysteine, act as precursors to increase the synthesis of endogenous antioxidants like glutathione [8].