Glutathione metabolism and Parkinson's disease

• Published in: Free radical biology & medicine 2013-09, Vol.62, p.13-25
• Main Authors: Smeyne, Michelle, Smeyne, Richard Jay
• Format: Article
• Language: English
• Subjects: antioxidant activity; Antioxidants - metabolism; Dopamine - metabolism; Dopaminergic Neurons; enzymes; Glutathione; Glutathione - metabolism; Glutathione S-transferase; Humans; hydroxyl radicals; metabolism; Mitochondria - enzymology; Mitochondria - metabolism; neurons; Oxidative Stress; Parkinson disease; Parkinson Disease - enzymology; Parkinson Disease - metabolism; Parkinson Disease - physiopathology; Parkinson's disease; pathogenesis; Substantia nigra; Substantia Nigra - enzymology; superoxide anion; thiols
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2013.05.001

It has been established that oxidative stress, defined as the condition in which the sum of free radicals in a cell exceeds the antioxidant capacity of the cell, contributes to the pathogenesis of Parkinson disease. Glutathione is a ubiquitous thiol tripeptide that acts alone or in concert with enzymes within cells to reduce superoxide radicals, hydroxyl radicals, and peroxynitrites. In this review, we examine the synthesis, metabolism, and functional interactions of glutathione and discuss how these relate to the protection of dopaminergic neurons from oxidative damage and its therapeutic potential in Parkinson disease. [Display omitted] •Glutathione, a thiol tripeptide, is an important antioxidant in the brain.•GSH is critical for protecting DA neurons in the SNpc from free radical damage.•GPx and GSTs catalyze the reduction of electrophiles using GSH.•GST mutations combined with environmental insults correlate with increased PD risk.•Maintaining GSH levels may provide a therapeutic treatment for PD.