Glutathione redox imbalance in brain disorders

Glutathione (GSH) is a major endogenous antioxidant. Several studies have implicated GSH redox imbalance in brain disorders. Here, we summarize current evidence on how GSH depletion and GSH-related enzyme deficit are involved in the pathology of brain disorders such as autism, schizophrenia, bipolar disorder, Alzheimer's disease, and Parkinson's disease.

Many studies with animal models of various brain disorders and/or with clinical samples from humans with neurodegenerative and neuropsychiatric disorders have demonstrated altered levels of GSH and oxidized glutathione (GSSG), decreased ratio of GSH/GSSG, and/or impaired expressions or activities of GSH-related enzymes in the blood or brain of these individuals. GSH depletion can lead to abnormalities in methylation metabolism and mitochondrial function. A few studies showed that a GSH deficit occurs prior to neuropathological abnormalities in these diseases. The potential therapeutic agents for brain disorders include N-acetylcysteine, liposomes encapsulated with GSH, and whey protein supplement, which can increase the GSH levels in the brain and alleviate oxidative stress-associated damage and may improve the behavior of individuals with brain diseases.

GSH plays an important role during the onset and progression of neuropsychiatric and neurodegenerative diseases. GSH redox imbalance may be a primary cause of these brain disorders and may be used as a biomarker for diagnosis of these diseases. N-acetylcysteine and other agents that can increase the concentration of GSH in the brain are promising approaches for the treatment of these brain disorders.