Redox control of neural function: background, mechanisms, and significance

The redox environment within neural cells is dependent on a series of redox couples. The glutathione disulfide/ glutathione (GSSG/GSH) redox pair forms the major redox couple in cells and as such plays a critical role in regulating redox-dependent cellular functions. Not only does GSH act as an antioxidant but it also can modulate the activity of a variety of different proteins via S-glutathionylation of cysteine sulfhydryl groups. The thioredoxin system also makes a significant contribution to the redox environment by reducing inter- and intrachain protein disulfide bonds as well as maintaining the activity of important antioxidant enzymes such as peroxiredoxins and methionine sulfoxide reductases. The redox environment affects the activity and function of a number of different protein phosphatases, protein kinases, and transcription factors. The sum of these effects will determine how changes in the redox environment alter overall cellular function, thereby playing a fundamental role in regulating neural cell fate and physiology.