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Dysregulation of glutathione homeostasis in neurodegenerative diseases.
Nutrients. 2012 Oct 09; 4(10):1399-440.N

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, 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.

Authors+Show Affiliations

Department of Pharmacology, Case Western Reserve University, 2109 Adelbert Rd, Cleveland, OH 44106, USA. wmj18@case.eduNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Review

Language

eng

PubMed ID

23201762

Citation

Johnson, William M., et al. "Dysregulation of Glutathione Homeostasis in Neurodegenerative Diseases." Nutrients, vol. 4, no. 10, 2012, pp. 1399-440.
Johnson WM, Wilson-Delfosse AL, Mieyal JJ. Dysregulation of glutathione homeostasis in neurodegenerative diseases. Nutrients. 2012;4(10):1399-440.
Johnson, W. M., Wilson-Delfosse, A. L., & Mieyal, J. J. (2012). Dysregulation of glutathione homeostasis in neurodegenerative diseases. Nutrients, 4(10), 1399-440. https://doi.org/10.3390/nu4101399
Johnson WM, Wilson-Delfosse AL, Mieyal JJ. Dysregulation of Glutathione Homeostasis in Neurodegenerative Diseases. Nutrients. 2012 Oct 9;4(10):1399-440. PubMed PMID: 23201762.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dysregulation of glutathione homeostasis in neurodegenerative diseases. AU - Johnson,William M, AU - Wilson-Delfosse,Amy L, AU - Mieyal,John J, Y1 - 2012/10/09/ PY - 2012/07/01/received PY - 2012/08/22/revised PY - 2012/09/24/accepted PY - 2012/12/4/entrez PY - 2012/12/4/pubmed PY - 2013/5/11/medline SP - 1399 EP - 440 JF - Nutrients JO - Nutrients VL - 4 IS - 10 N2 - 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. SN - 2072-6643 UR - https://www.unboundmedicine.com/medline/citation/23201762/Dysregulation_of_glutathione_homeostasis_in_neurodegenerative_diseases_ L2 - http://www.mdpi.com/resolver?pii=nu4101399 DB - PRIME DP - Unbound Medicine ER -