Thioredoxin-related redox and inflammatory signaling pathways (Trx system)

The Thioredoxin-related redox and inflammatory signaling pathways constitute a fundamental cellular system responsible for maintaining thiol-disulfide homeostasis and regulating the response to oxidative stress (PMID: 28213285). Centered around Thioredoxin (Trx), Thioredoxin Reductase (TrxR), and Thioredoxin-interacting protein (TXNIP), this system facilitates DNA synthesis by providing reducing equivalents to ribonucleotide reductase and modulates various transcription factors like NF-κB and p53 (PMID: 22449905, PMID: 19769458). In disease states, particularly cancer, the system is often upregulated to protect malignant cells from oxidative damage and promote survival, making it a significant target for chemotherapy (PMID: 22449905). Furthermore, TXNIP acts as a critical bridge between redox status and the innate immune response by activating the NLRP3 inflammasome, making it a key player in inflammatory diseases such as type 2 diabetes and atherosclerosis (PMID: 20023630). Pharmacological targeting typically involves small-molecule inhibitors of TrxR, such as auranofin, which disrupt the redox balance to induce apoptosis in tumor cells or mitigate chronic inflammation (PMID: 15607520, PMID: 21217704). Overall, this pathway represents a versatile therapeutic target for both oncology and inflammatory disorders.

Other names

Thioredoxin systemTrx/TrxR/TXNIP pathwayRedox-regulated signaling networkThiol-dependent antioxidant system

Inhibition of thioredoxin reductase (TrxR) activity, leading to the accumulation of oxidized thioredoxin, increased reactive oxygen species (ROS), and induction of apoptosis; or modulation of TXNIP to inhibit NLRP3 inflammasome activation (PMID: 15607520, PMID: 20023630).