15 Glutathione in the Nervous System: Roles in Neural Function and Health and Implications for Neurological Disease


Glutathione (γ-l-glutamyl-l-cysteinylglycine, GSH) is the most abundant cellular antioxidant molecule in aerobic cells. In the nervous system, it is found in the millimolar range in both neuronal and nonneuronal cells, arising endogenously by synthesis from its precursor amino acids or taken up from the blood by means of specific transport mechanisms. Glutathione can participate as an antioxidant either as a substrate of glutathione peroxidase (GSHPx) or as an electron donor in spontaneous reactions with reactive oxygen species (ROS). Besides the well-established role of glutathione as an antioxidant, it serves other functions in the nervous system, including neutralization of xenobiotics, participation in amino acid transport, regulation of the activity and conformation of proteins, protection against cysteine and glutamate neurotoxicities, and modulation of glutamatergic transmission. In addition, several lines of evidence suggest that glutathione might act as a neurotransmitter on its own class of receptors. This latter possibility may have significant implications for the possible involvement of GSH in learning and memory processes. Given its ample range of functions in the nervous system, it is not surprising to find significant alterations in glutathione levels and/or glutathione-related enzymes during brain aging and in several neurological conditions including Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), schizophrenia, and chronic fatigue syndrome (CFS).