Cellular sulfhydryl-containing redox systems

Cellular sulfhydryl-containing redox systems, primarily the glutathione (GSH) and thioredoxin (Trx) systems, are essential for maintaining intracellular redox homeostasis and protecting cells from oxidative damage. These systems utilize the chemical reactivity of the sulfhydryl (-SH) group in cysteine residues to neutralize reactive oxygen species (ROS), facilitate proper protein folding, and regulate signal transduction through redox-sensitive molecular switches. In many pathological states, particularly cancer, these systems are upregulated to support rapid proliferation and confer resistance to therapy, whereas their impairment is linked to neurodegeneration, cardiovascular disease, and aging. Pharmacological intervention involves either the inhibition of these systems to sensitize diseased cells (e.g., using thioredoxin reductase inhibitors like auranofin) or the replenishment of thiol pools to mitigate oxidative damage (e.g., using N-acetylcysteine). Because these systems are ubiquitous and vital for normal cell function, targeting them requires careful consideration of the therapeutic index and potential for systemic toxicity.

Other names

Thiol-based redox systemsCellular thiol systemsGlutathione and thioredoxin systemsProtein sulfhydryl groupsThiol-disulfide exchange systems

Inhibition of redox enzymes (e.g., thioredoxin reductase, glutathione reductase), depletion of low-molecular-weight thiol pools (e.g., GSH), covalent modification of cysteine residues, or replenishment of antioxidant capacity.