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Int. J. Mol. Sci. 2012, 13(9), 12017-12035; doi:10.3390/ijms130912017

Inhibition of GTRAP3-18 May Increase Neuroprotective Glutathione (GSH) Synthesis

Department of Pharmacology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan
* Author to whom correspondence should be addressed.
Received: 9 July 2012 / Revised: 6 August 2012 / Accepted: 10 September 2012 / Published: 20 September 2012
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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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.
Keywords: glutathione; cysteine uptake; GTRAP3-18; EAAC1; neurodegeneration glutathione; cysteine uptake; GTRAP3-18; EAAC1; neurodegeneration
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Aoyama, K.; Nakaki, T. Inhibition of GTRAP3-18 May Increase Neuroprotective Glutathione (GSH) Synthesis. Int. J. Mol. Sci. 2012, 13, 12017-12035.

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