ReviewAntioxidants & redox signaling2013
Thioredoxin glutathione reductase-dependent redox networks in platyhelminth parasites.
Review in Antioxidants & redox signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 74 citations in OpenAlex.
- Structural basis for substrate recognition and inhibition of thioredoxin glutathione reductase from Schistosoma japonicum: Implications for antiparasitic development.PLoS pathogens · 2026Article
- Screening Novel Furoxan Derivatives as Potential Inhibitors Targeting Thioredoxin Glutathione Reductase ofPharmaceuticals (Basel, Switzerland) · 2025Article
- Review
- The "Doorstop Pocket" In Thioredoxin Reductases─An Unexpected Druggable Regulator of the Catalytic Machinery.Journal of medicinal chemistry · 2024Review
- A Physiological Approach to Explore How Thioredoxin-Glutathione Reductase (TGR) and Peroxiredoxin (Prx) Eliminate HAntioxidants (Basel, Switzerland) · 2024Article
- Fragment library screening by X-ray crystallography and binding site analysis on thioredoxin glutathione reductase of Schistosoma mansoni.Scientific reports · 2024Article
- In silico design of an epitope-based vaccine ensemble for fasliolopsiasis.Frontiers in genetics · 2024Article
- A genome-scale metabolic model of parasitic whipworm.Nature communications · 2023Article
- Non-covalent inhibitors of thioredoxin glutathione reductase with schistosomicidal activity in vivo.Nature communications · 2023Article
- Assigning function to active site residues ofFrontiers in molecular biosciences · 2023Article
- Hypoxia reveals a new function of Foxn1 in the keratinocyte antioxidant defense system.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Evolutionary Adaptations of Parasitic Flatworms to Different Oxygen Tensions.Antioxidants (Basel, Switzerland) · 2022Review
- Biochemical and structural characterizations of thioredoxin reductase selenoproteins of the parasitic filarial nematodes Brugia malayi and Onchocerca volvulus.Redox biology · 2022Article
- Probing the Surface of a Parasite Drug Target Thioredoxin Glutathione Reductase Using Small Molecule Fragments.ACS infectious diseases · 2021Article
- Selenium as a Bioactive Micronutrient in the Human Diet and Its Cancer Chemopreventive Activity.Nutrients · 2021Review
- Repurposing Auranofin and Evaluation of a New Gold(I) Compound for the Search of Treatment of Human and Cattle Parasitic Diseases: From Protozoa to Helminth Infections.Molecules (Basel, Switzerland) · 2020Article
- Characterization of Lead Compounds Targeting the Selenoprotein Thioredoxin Glutathione Reductase for Treatment of Schistosomiasis.ACS infectious diseases · 2020Article
- Ectopic suicide inhibition of thioredoxin glutathione reductase.Free radical biology & medicine · 2020Article
- Unraveling oxidative stress response in the cestode parasite Echinococcus granulosus.Scientific reports · 2019Article
- Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
Abstract
significancePlatyhelminth parasites cause chronic infections that are a major cause of disability, mortality, and economic losses in developing countries. Maintaining redox homeostasis is a major adaptive problem faced by parasites and its disruption can shift the biochemical balance toward the host. Platyhelminth parasites possess a streamlined thiol-based redox system in which a single enzyme, thioredoxin glutathione reductase (TGR), a fusion of a glutaredoxin (Grx) domain to canonical thioredoxin reductase (TR) domains, supplies electrons to oxidized glutathione (GSSG) and thioredoxin (Trx). TGR has been validated as a drug target for schistosomiasis. RECENT ADVANCES: In addition to glutathione (GSH) and Trx reduction, TGR supports GSH-independent deglutathionylation conferring an additional advantage to the TGR redox array. Biochemical and structural studies have shown that the TR activity does not require the Grx domain, while the glutathione reductase and deglutathionylase activities depend on the Grx domain, which receives electrons from the TR domains. The search for TGR inhibitors has identified promising drug leads, notably oxadiazole N-oxides. CRITICAL ISSUES: A conspicuous feature of platyhelminth TGRs is that their Grx-dependent activities are temporarily inhibited at high GSSG concentrations. The mechanism underlying the phenomenon and its biological relevance are not completely understood. FUTURE DIRECTIONS: The functional diversity of Trxs and Grxs encoded in platyhelminth genomes remains to be further assessed to thoroughly understand the TGR-dependent redox network. Optimization of TGR inhibitors and identification of compounds targeting other parasite redox enzymes are good options to clinically develop relevant drugs for these neglected, but important diseases.
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