Reactive oxygen species and glutathione-related antioxidant systems (ROS-GSH system)

The reactive oxygen species (ROS) and glutathione-related antioxidant systems constitute a fundamental biological network responsible for maintaining cellular redox homeostasis. ROS, such as superoxide and hydrogen peroxide, are metabolic byproducts that serve as essential signaling molecules at low levels but cause damage to DNA, lipids, and proteins when in excess [1]. The glutathione (GSH) system, comprising the tripeptide GSH and enzymes like glutathione peroxidase (GPx) and glutathione reductase (GR), acts as the primary defense by neutralizing ROS and maintaining a reduced cellular environment [2]. Dysregulation of this system is a hallmark of various pathologies; for instance, cancer cells often upregulate GSH production to survive high metabolic ROS and resist therapy [3]. Consequently, therapeutic strategies include the use of GSH-depleting agents or GPX4 inhibitors to trigger ferroptosis in tumors [4]. In contrast, for neurodegenerative and cardiovascular diseases, the goal is often to enhance the system using precursors like N-acetylcysteine to mitigate oxidative damage [5]. Because this target encompasses a broad metabolic pathway rather than a single receptor, drug development faces challenges in achieving specificity without disrupting vital physiological signaling [6].

Other names

Redox homeostasis systemGlutathione metabolic pathwayROS scavenging systemGSH-ROS axisCellular antioxidant defense system

Modulation of cellular redox state through the replenishment of antioxidant pools, mimicry of antioxidant enzymes, or the targeted inhibition of glutathione synthesis and utilization to induce oxidative stress-mediated cell death.