ABSTRACT
This chapter provides a summary of the knowledge on the interplay between glutaredoxins (Grx), glutathione (GSH), and iron in the context of the central nervous system. Grxs belong to the thioredoxin (Trx) family, which is characterized by a common structural fold named the Trx-fold consisting of a central 4–5-stranded ß-sheet surrounded by 3–4 a-helices. Grxs regulate deglutathionylation and thiol–disulfide switches. Dysregulation of these posttranslational modifications is associated with numerous aspects of neurodegeneration like apoptosis and plaque formation. Pathways that were previously proven to be regulated in a Grx-dependent manner were found to be altered upon inflammation-related brain disorders. Many diseases of the central nervous system are accompanied by iron accumulation. Iron accumulates during normal aging in deposits in human brains; however, in diseased brains, this accumulation is accelerated and more prominent. Accelerated GSH depletion or a shift towards Oxidized GSH (GSSG) is associated with a variety of diseases and especially brain disorders including Alzheimer's disease.
