Inhibition of thioredoxin reductase in treatment of nitric oxide deficiency
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.
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