International Journal of Molecular Sciences | |
Inhibition of GTRAP3-18 May Increase Neuroprotective Glutathione (GSH) Synthesis | |
Koji Aoyama1  | |
[1] Department of Pharmacology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan; E-Mail | |
关键词: glutathione; cysteine uptake; GTRAP3-18; EAAC1; neurodegeneration; | |
DOI : 10.3390/ijms130912017 | |
来源: mdpi | |
【 摘 要 】
Glutathione (GSH) is a tripeptide consisting of glutamate, cysteine, and glycine; it has a variety of functions in the central nervous system. Brain GSH depletion is considered a preclinical sign in age-related neurodegenerative diseases, and it promotes the subsequent processes toward neurotoxicity. A neuroprotective mechanism accomplished by increasing GSH synthesis could be a promising approach in the treatment of neurodegenerative diseases. In neurons, cysteine is the rate-limiting substrate for GSH synthesis. Excitatory amino acid carrier 1 (EAAC1) is a neuronal cysteine/glutamate transporter in the brain. EAAC1 translocation to the plasma membrane promotes cysteine uptake, leading to GSH synthesis, while being negatively regulated by glutamate transport associated protein 3-18 (GTRAP3-18). Our recent studies have suggested GTRAP3-18 as an inhibitory factor for neuronal GSH synthesis. Inhibiting GTRAP3-18 function is an endogenous mechanism to increase neuron-specific GSH synthesis in the brain. This review gives an overview of EAAC1-mediated GSH synthesis, and its regulatory mechanisms by GTRAP3-18 in the brain, and a potential approach against neurodegeneration.
【 授权许可】
CC BY
© 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.
【 预 览 】
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RO202003190041794ZK.pdf | 1048KB | download |