Thioredoxin redox system (Trx system)

The thioredoxin redox system is a major cellular antioxidant system consisting of thioredoxin (Trx), the selenoenzyme thioredoxin reductase (TrxR), and NADPH (Lu & Holmgren, 2014). It plays a pivotal role in maintaining a reduced intracellular environment by facilitating the reduction of protein disulfides and providing reducing equivalents for DNA synthesis via ribonucleotide reductase (Arnér & Holmgren, 2000). In oncology, the system is frequently overexpressed, allowing cancer cells to resist oxidative stress-induced apoptosis and promoting tumor progression and chemoresistance (Zhang et al., 2017). Therapeutic strategies targeting this system primarily involve small molecule inhibitors like auranofin and PX-12, which bind to the active sites of TrxR or Trx to disrupt redox signaling (Stafford et al., 2018). By inhibiting these components, drugs induce a lethal accumulation of reactive oxygen species (ROS) specifically in cancer cells, which are more dependent on this system than healthy cells (Gandin et al., 2014). Beyond its role in cancer, the system is involved in regulating transcription factors such as NF-kappaB and p53, influencing cell survival and inflammatory pathways (Karlenius & Tonissen, 2010). The system also serves as a critical defense mechanism against neurodegeneration by mitigating oxidative damage in the central nervous system (Lillig & Holmgren, 2007).

Other names

Thioredoxin-thioredoxin reductase systemTrx/TrxR systemTXN system

Inhibition of thioredoxin reductase (TrxR) or thioredoxin (Trx) to disrupt cellular redox balance, leading to increased reactive oxygen species (ROS) and induction of apoptosis (Stafford et al., 2018).