Thioredoxin-1 redox system (Trx1 system)

The Thioredoxin-1 (Trx1) redox system is a fundamental cellular antioxidant network comprising Thioredoxin-1, Thioredoxin reductase 1 (TrxR1), and NADPH (NIH, 2013; MDPI, 2023). It plays a critical role in maintaining cellular redox homeostasis by reducing oxidized proteins and scavenging reactive oxygen species (ROS) through peroxiredoxins (Wikipedia, 2024; NIH, 2024). In addition to its antioxidant function, the system regulates key signaling pathways involved in cell proliferation, DNA synthesis, and apoptosis, often by modulating the activity of transcription factors like NF-κB and AP-1 (NIH, 2023; ResearchGate, 2022). In many cancers, the Trx1 system is overexpressed, contributing to tumor growth, survival, and resistance to chemotherapy, making it a prominent target for anticancer drug development (NIH, 2013; NIH, 2021). Conversely, its protective role in healthy tissues suggests potential therapeutic applications for its activators in cardiovascular and neurodegenerative diseases (NIH, 2022; NIH, 2025).

Other names

Thioredoxin systemTrx systemTXN systemThioredoxin/thioredoxin reductase systemTrx1/TrxR1 system

The system is targeted primarily through the inhibition of its enzymatic components, specifically Thioredoxin reductase 1 (TrxR1) and Thioredoxin-1 (Trx1) (NIH, 2021). Inhibition leads to the accumulation of oxidized thioredoxin and reactive oxygen species (ROS), which triggers oxidative stress-mediated apoptosis, particularly in cancer cells that are highly dependent on this system for survival (NIH, 2013). Some drugs also act by disrupting the interaction between Trx1 and its regulatory partners like ASK1, thereby promoting pro-apoptotic signaling (NIH, 2023).