Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/ijms22095010
Keywords
glutathione; cysteine; excitatory amino acid carrier 1; glutamate transporter-associated protein 3-18; miR-96-5p; neurodegeneration
Funding
- Teijin Pharma
- Kao Corporation
- Japan Blood Products Organization
- Eli Lilly Japan
- Tsumura
- Sanofi
- MSD
- Daiichi-Sankyo
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Glutathione (GSH) depletion in neurons is common in neurodegenerative diseases and can lead to neurodegeneration. Excitatory amino acid carrier 1 (EAAC1) plays a central role in regulating neuronal GSH production, making it a potential target for therapeutic strategies in these diseases.
Glutathione (GSH) is the most abundant non-protein thiol, and plays crucial roles in the antioxidant defense system and the maintenance of redox homeostasis in neurons. GSH depletion in the brain is a common finding in patients with neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, and can cause neurodegeneration prior to disease onset. Excitatory amino acid carrier 1 (EAAC1), a sodium-dependent glutamate/cysteine transporter that is selectively present in neurons, plays a central role in the regulation of neuronal GSH production. The expression of EAAC1 is posttranslationally controlled by the glutamate transporter-associated protein 3-18 (GTRAP3-18) or miR-96-5p in neurons. The regulatory mechanism of neuronal GSH production mediated by EAAC1 may be a new target in therapeutic strategies for these neurodegenerative diseases. This review describes the regulatory mechanism of neuronal GSH production and its potential therapeutic application in the treatment of neurodegenerative diseases.
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