{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThioredoxin (TXN) is a ubiquitous redox-active protein that functions as a potent disulfide reductase, modulating the redox state of numerous intracellular targets. It catalyzes reversible thiol–disulfide exchange reactions and plays a critical role in maintaining cellular redox homeostasis. TXN regulates protein function via precise active‐site geometry control and through dynamic modifications such as S‑nitrosylation and glutathionylation, which affect its enzymatic activity and interactions with downstream effectors (for example, caspase-3, ASK1, and peroxiredoxins). In particular, TXN functions as a denitrosylase, removing S-nitrosylation from proteins to restore their activity, and its activity can be modulated via non-active site disulfide formation that transiently inhibits reduction activity during redox signaling events."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTXN also plays multifaceted roles in pathophysiological contexts. In oncogenesis, overexpression of TXN is often associated with enhanced tumor cell growth, survival, invasion, and chemoresistance, while its transcription is tightly regulated by stress-responsive factors such as Nrf2 and DJ-1. In contrast, in conditions marked by excessive oxidative stress—such as diabetes, atherosclerosis, neurodegeneration, and cardiac ischemia—TXN exerts cytoprotective, antiapoptotic, and anti-inflammatory effects. However, its function can be inhibited by endogenous proteins like TXN-interacting protein (TXNIP) or altered by deleterious post-translational modifications (such as nitration), leading to impaired ROS scavenging and dysregulated signaling that contribute to disease progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "38"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its intracellular roles, TXN is also secreted and participates in extracellular redox signaling and intercellular communication. It can directly interact with specific cell-surface receptors—modulating ligand binding and downstream signaling cascades through transnitrosylation reactions—as well as serve as a backup antioxidant system when classical reducing enzymes (such as thioredoxin reductases) are compromised. 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