Glutathione in Brain: Overview of Its Conformations, Functions, Biochemical Characteristics, Quantitation and Potential Therapeutic Role in Brain Disorders

Glutathione (GSH) is an important antioxidant found abundantly and synthesized intracellularly in the cytosol in a tightly regulated fashion. It has diverse physiological functions, including protection against reactive oxygen species and nitrogen species, antioxidant defense as well as maintenance of cellular thiol status. The human brain due to the high oxygen consumption is extremely susceptible to the generation of reactive oxygen species. GSH plays a paramount role in brain antioxidant defense, maintaining redox homeostasis. The depletion of brain GSH has also been observed from both autopsies as well as in vivo MRS studies with aging and varied neurological disorders (Alzheimer's disease, Parkinson's disease, etc.). Therefore, GSH enrichment using supplementation is a promising avenue in the therapeutic development for these neurological disorders. This review will enrich the information on the importance of GSH synthesis, metabolism, functions, compartmentation and inter-organ transport, structural conformations and its quantitation via different techniques. The transportation of GSH in the brain via different interventional routes and its potential role in the development of therapeutic strategies for various brain disorders is also addressed. Very recent study found significant improvement of behavioral deficits including cognitive decline, depressive-like behaviors, in APP (NL-G-F/NL-G-FG-) mice due to oral GSH administration. This animal model study put an emergent need to complete GSH supplementation trial in MCI and AD patients for cognitive improvement as proposed earlier.