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Glutathione
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Glutathione

A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (31 January 2012) | Viewed by 21507

Special Issue Editors

Prof. Dr. Dean P. Jones

E-Mail Website
Guest Editor
Department of Medicine, Emory University, 615 Michael Street, NW, Suite 205P, Atlanta, GA 30322, USA
Interests: molecular toxicology, with an emphasis on the role of mitochondria in apoptosis and nutritional approaches to enhance GSH-dependent detoxification systems
Prof. Dr. Peter J. O'Brien

E-Mail Website
Guest Editor
Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada
Interests: Mechanisms of Drug-Induced Cytotoxicity and Its Prevention

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Review

42 pages, 1041 KiB  
Review
Dysregulation of Glutathione Homeostasis in Neurodegenerative Diseases
by William M. Johnson, Amy L. Wilson-Delfosse and John. J. Mieyal
Nutrients 2012, 4(10), 1399-1440; https://doi.org/10.3390/nu4101399 - 9 Oct 2012
Cited by 300 | Viewed by 20859
Abstract
Dysregulation of glutathione homeostasis and alterations in glutathione-dependent enzyme activities are increasingly implicated in the induction and progression of neurodegenerative diseases, including Alzheimer’s, Parkinson’s and Huntington’s diseases, amyotrophic lateral sclerosis, and Friedreich’s ataxia. In this review background is provided on the steady-state synthesis, [...] Read more.
Dysregulation of glutathione homeostasis and alterations in glutathione-dependent enzyme activities are increasingly implicated in the induction and progression of neurodegenerative diseases, including Alzheimer’s, Parkinson’s and Huntington’s diseases, amyotrophic lateral sclerosis, and Friedreich’s ataxia. In this review background is provided on the steady-state synthesis, regulation, and transport of glutathione, with primary focus on the brain. A brief overview is presented on the distinct but vital roles of glutathione in cellular maintenance and survival, and on the functions of key glutathione-dependent enzymes. Major contributors to initiation and progression of neurodegenerative diseases are considered, including oxidative stress, protein misfolding, and protein aggregation. In each case examples of key regulatory mechanisms are identified that are sensitive to changes in glutathione redox status and/or in the activities of glutathione-dependent enzymes. Mechanisms of dysregulation of glutathione and/or glutathione-dependent enzymes are discussed that are implicated in pathogenesis of each neurodegenerative disease. Limitations in information or interpretation are identified, and possible avenues for further research are described with an aim to elucidating novel targets for therapeutic interventions. The pros and cons of administration of N-acetylcysteine or glutathione as therapeutic agents for neurodegenerative diseases, as well as the potential utility of serum glutathione as a biomarker, are critically evaluated. Full article
(This article belongs to the Special Issue Glutathione)
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