Impaired Glutathione Synthesis in Neurodegeneration

Glutathione (GSH) was discovered in yeast cells in 1888. Studies of GSH in mammalian cells before the 1980s focused exclusively on its function for the detoxication of xenobiotics or for drug metabolism in the liver, in which GSH is present at its highest concentration in the body. Increasing eviden...

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Main Authors: Toshio Nakaki, Koji Aoyama
Format: Article
Language:English
Published: MDPI AG 2013-10-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:http://www.mdpi.com/1422-0067/14/10/21021
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spelling doaj-f4a47d1a095b4eddb6cc8417024425072020-11-25T01:47:05ZengMDPI AGInternational Journal of Molecular Sciences1422-00672013-10-011410210212104410.3390/ijms141021021Impaired Glutathione Synthesis in NeurodegenerationToshio NakakiKoji AoyamaGlutathione (GSH) was discovered in yeast cells in 1888. Studies of GSH in mammalian cells before the 1980s focused exclusively on its function for the detoxication of xenobiotics or for drug metabolism in the liver, in which GSH is present at its highest concentration in the body. Increasing evidence has demonstrated other important roles of GSH in the brain, not only for the detoxication of xenobiotics but also for antioxidant defense and the regulation of intracellular redox homeostasis. GSH also regulates cell signaling, protein function, gene expression, and cell differentiation/proliferation in the brain. Clinically, inborn errors in GSH-related enzymes are very rare, but disorders of GSH metabolism are common in major neurodegenerative diseases showing GSH depletion and increased levels of oxidative stress in the brain. GSH depletion would precipitate oxidative damage in the brain, leading to neurodegenerative diseases. This review focuses on the significance of GSH function, the synthesis of GSH and its metabolism, and clinical disorders of GSH metabolism. A potential approach to increase brain GSH levels against neurodegeneration is also discussed.http://www.mdpi.com/1422-0067/14/10/21021glutathionecysteine transportoxidative stressneurodegenerationEAAC1GTRAP3-18
collection DOAJ
language English
format Article
sources DOAJ
author Toshio Nakaki
Koji Aoyama
spellingShingle Toshio Nakaki
Koji Aoyama
Impaired Glutathione Synthesis in Neurodegeneration
International Journal of Molecular Sciences
glutathione
cysteine transport
oxidative stress
neurodegeneration
EAAC1
GTRAP3-18
author_facet Toshio Nakaki
Koji Aoyama
author_sort Toshio Nakaki
title Impaired Glutathione Synthesis in Neurodegeneration
title_short Impaired Glutathione Synthesis in Neurodegeneration
title_full Impaired Glutathione Synthesis in Neurodegeneration
title_fullStr Impaired Glutathione Synthesis in Neurodegeneration
title_full_unstemmed Impaired Glutathione Synthesis in Neurodegeneration
title_sort impaired glutathione synthesis in neurodegeneration
publisher MDPI AG
series International Journal of Molecular Sciences
issn 1422-0067
publishDate 2013-10-01
description Glutathione (GSH) was discovered in yeast cells in 1888. Studies of GSH in mammalian cells before the 1980s focused exclusively on its function for the detoxication of xenobiotics or for drug metabolism in the liver, in which GSH is present at its highest concentration in the body. Increasing evidence has demonstrated other important roles of GSH in the brain, not only for the detoxication of xenobiotics but also for antioxidant defense and the regulation of intracellular redox homeostasis. GSH also regulates cell signaling, protein function, gene expression, and cell differentiation/proliferation in the brain. Clinically, inborn errors in GSH-related enzymes are very rare, but disorders of GSH metabolism are common in major neurodegenerative diseases showing GSH depletion and increased levels of oxidative stress in the brain. GSH depletion would precipitate oxidative damage in the brain, leading to neurodegenerative diseases. This review focuses on the significance of GSH function, the synthesis of GSH and its metabolism, and clinical disorders of GSH metabolism. A potential approach to increase brain GSH levels against neurodegeneration is also discussed.
topic glutathione
cysteine transport
oxidative stress
neurodegeneration
EAAC1
GTRAP3-18
url http://www.mdpi.com/1422-0067/14/10/21021
work_keys_str_mv AT toshionakaki impairedglutathionesynthesisinneurodegeneration
AT kojiaoyama impairedglutathionesynthesisinneurodegeneration
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