Cellular redox systems and glutathione pool (GSH system)

The cellular redox systems and glutathione pool represent a complex network of enzymes and molecules dedicated to maintaining oxidative homeostasis and protecting cells from reactive oxygen species (ROS). The glutathione (GSH) pool is the primary endogenous antioxidant system, consisting of the tripeptide GSH, its oxidized form GSSG, and enzymes such as glutathione peroxidase (GPX) and glutathione reductase (GSR). These systems are critical for detoxifying xenobiotics, regulating protein function through thiol-disulfide exchange, and modulating signal transduction pathways related to cell survival and death. In many diseases, particularly cancer, these systems are upregulated to protect malignant cells from high metabolic stress and chemotherapy-induced ROS, making them attractive targets for therapeutic intervention. Conversely, in neurodegenerative and cardiovascular diseases, boosting the glutathione pool is often a strategy to mitigate oxidative damage. While 'Cellular redox systems and glutathione pool' is a broad biological category rather than a single molecular target, it encompasses specific druggable components like the xCT transporter (SLC7A11) and glutamate-cysteine ligase (GCL).

Other names

Glutathione metabolismRedox homeostasisGlutathione antioxidant systemThiol-based redox systemsGSH/GSSG pool

Drugs targeting this system typically act by depleting glutathione levels (e.g., inhibiting glutamate-cysteine ligase or the xCT transporter), inhibiting antioxidant enzymes (e.g., glutathione peroxidase or thioredoxin reductase), or providing precursors to boost antioxidant capacity (e.g., NAC).