Inhibition of thioredoxin reductase in treatment of nitric oxide deficiency

Value Proposition

One of the signaling mechanisms mediated by nitric oxide is through S-nitrosylation modification of cysteine residues. Dysregulated protein S-nitrosylation is implicated in the pathogenesis of several diseases including neurodegenerative diseases. Accordingly, therapeutic agents that modulate nitrosylation could offer new treatment strategy for a significant number of diseases.


Researchers at Duke have developed a novel therapeutic approach to treat diseases that involve abnormal S-nitrosylation of the apoptotic pathway. Propagation of the apoptotic signal requires thioredoxin reductase 2-mediated denitrosylation of caspase-3. Accordingly, treatment with auranofin, an inhibitor of thioredoxin reductase 2, abrogates denitrosylation and enhances cell survival. Notably, treatment of cells with auranofin, resulted in a significant decrease in the proportion of apoptotic cells.

Other Applications

Caspase inhibition can help ameliorate the symptoms of several other conditions caused by inappropriate apoptotic cell death including ischemia reperfusion injury


  • Targets diseases in which deficiency of S-nitrosylation is implicated
  • Can potentially inhibit neuronal death in a variety of neurodegenerative diseases, including Alzheimer’s disease

Duke File (IDF) Number



  • Stamler, Jonathan
  • Benhar, Moran

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School of Medicine (SOM)