{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:30:43Z","timestamp":1790937043702,"version":"4.1.0"},"reference-count":198,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2012,10,9]],"date-time":"2012-10-09T00:00:00Z","timestamp":1349740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Dysregulation of glutathione homeostasis and alterations in glutathione-dependent enzyme activities are increasingly implicated in the induction and progression of neurodegenerative diseases, including Alzheimer\u2019s, Parkinson\u2019s and Huntington\u2019s diseases, amyotrophic lateral sclerosis, and Friedreich\u2019s 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.<\/jats:p>","DOI":"10.3390\/nu4101399","type":"journal-article","created":{"date-parts":[[2012,10,10]],"date-time":"2012-10-10T02:55:18Z","timestamp":1349837718000},"page":"1399-1440","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":313,"title":["Dysregulation of Glutathione Homeostasis in Neurodegenerative Diseases"],"prefix":"10.3390","volume":"4","author":[{"given":"William M.","family":"Johnson","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Case Western Reserve University, 2109 Adelbert Rd., Cleveland, OH 44106, USA"},{"name":"Louis B. Stokes Veterans Affairs Medical Research Center, 10701 East Blvd, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy L.","family":"Wilson-Delfosse","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Case Western Reserve University, 2109 Adelbert Rd., Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John. J.","family":"Mieyal","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Case Western Reserve University, 2109 Adelbert Rd., Cleveland, OH 44106, USA"},{"name":"Louis B. Stokes Veterans Affairs Medical Research Center, 10701 East Blvd, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2012,10,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0009-2797(97)00146-4","article-title":"Glutathione: An overview of biosynthesis and modulation","volume":"111-112","author":"Anderson","year":"1998","journal-title":"Chem. Biol. 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