Thioredoxin glutathione reductase: its role in redox biology and potential as a target for drugs against neglected diseases.

There are two, largely autonomous antioxidant pathways in many organisms, one based on thioredoxin and one based on glutathione, with each pathway having a unique flavoprotein oxidoreductase to maintain them in a reduced state. A recently discovered protein, thioredoxin glutathione reductase (TGR) potentially connects these two pathways. In a large group of parasitic worms, responsible for hundreds of millions of infections in humans and animals, untold morbidity and significant mortality, TGR is the sole enzyme present to maintain redox balance. In this review, the current understanding of the biochemical properties of TGR enzymes is compared to the related enzymes thioredoxin reductase and glutathione reductase. The role of the rare amino acid selenocysteine is discussed. An overview of the potential to target TGR for drug development against a range of parasitic worms and preliminary results to identify TGR inhibitors for schistosomiasis treatment is presented. TGR has properties that are both unique and common to other flavoprotein oxidoreductases. TGR plays a fundamentally different and essential role in the redox biology of parasitic flatworms. Therefore, TGR is a promising target for drug development for schistosomiasis and other trematode and cestode infections. TGR may have differing functions in host organisms, but through analyses to understand its ability to reduce both glutathione and thioredoxin we can better understand the reaction mechanisms of an important class of enzymes. The unique properties of TGR in parasitic flatworms provide promising routes to develop new treatments for diseases. 2011 Elsevier B.V. All rights reserved.

Citation

Stefanie Prast-Nielsen, Hsin-Hung Huang, David L Williams. Thioredoxin glutathione reductase: its role in redox biology and potential as a target for drugs against neglected diseases. Biochimica et biophysica acta. 2011 Dec;1810(12):1262-71

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PMID: 21782895

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