Cellular redox-sensitive proteins and glutathione-dependent pathways

Cellular redox-sensitive proteins and glutathione-dependent pathways represent a broad biological system rather than a single molecular entity, comprising a network of enzymes and signaling molecules that maintain intracellular redox homeostasis. The glutathione (GSH) system is a cornerstone of this network, utilizing enzymes such as glutathione peroxidase (GPX) and glutathione S-transferase (GST) to neutralize reactive oxygen species (ROS) and detoxify xenobiotics (PubChem, CID 124886). Redox-sensitive proteins, particularly the Nrf2 (NFE2L2) transcription factor and its regulator Keap1, serve as sensors that activate the antioxidant response element (ARE) to induce the expression of protective genes (PubMed, PMID 29033367). Dysregulation of these pathways is a hallmark of various diseases; for instance, cancer cells often upregulate GSH to resist chemotherapy, while impaired redox signaling contributes to neurodegeneration and cardiovascular disease (NIH, PMC4684116). Therapeutic interventions include Nrf2 activators like dimethyl fumarate for multiple sclerosis and glutathione-depleting agents like buthionine sulfoximine (BSO) for cancer sensitization (PubMed, PMID 22503473).

Other names

Redox signaling pathwaysGlutathione systemAntioxidant defense systemThiol-redox network

Modulation of the Nrf2-Keap1 pathway to induce antioxidant gene expression, replenishment of intracellular glutathione pools, or inhibition of glutathione synthesis and utilization enzymes.