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Thioredoxin reductase as a pharmacological target.
Geir Bjørklund1, Lili Zou2, Jun Wang2
1Council for Nutritional and Environmental Medicine, Mo i Rana, Norway.
Thioredoxin reductases (TrxRs) are key antioxidant enzymes. Inhibiting TrxRs offers a promising therapeutic strategy for diseases involving redox imbalance, targeting their function or interactions.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Thioredoxin reductases (TrxRs) are crucial enzymes in the pyridine nucleotide disulfide oxidoreductase family.
- The TrxR-Trx system is a primary cellular antioxidant pathway regulating redox homeostasis.
- This system utilizes a disulfide-dithiol exchange mechanism involving TrxR, Trx, and NADPH.
Purpose of the Study:
- To review the cellular functions of TrxRs.
- To explore TrxR inhibition mechanisms by metal ions and chemicals.
- To update the understanding of TrxR gene involvement in human diseases.
Main Methods:
- Literature review and analysis of TrxR functions and inhibition.
- Examination of TrxR targeting strategies (direct, substrate, or interactor).
- Compilation of human diseases associated with TrxR genes using GWAS and literature data.
Main Results:
- TrxRs play critical roles in cellular redox balance.
- Various metal ions and chemicals can inhibit TrxR activity through different mechanisms.
- Dysregulation or overactivation of TrxRs is linked to numerous human pathologies.
Conclusions:
- TrxR inhibition is a significant clinical objective for redox-perturbed conditions.
- TrxRs are validated as critical therapeutic targets.
- There is substantial ongoing interest in developing novel TrxR-inhibiting molecules.
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