Loss of the gene for a neuronal glutamate transporter-binding protein induces glutathione synthesis and better cognitive performances in mice.

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Glutathione (GSH) plays some important neuroprotective roles in the brain. The strategy to increase neuronal GSH level in the brain is a promising approach to the treatment of neurodegenerative diseases. To investigate the potential regulatory mechanism to increase neuronal GSH level in vivo, we generated GTRAP3-18-deficient (GTRAP3-18 KO) mice using a gene-targeting approach. Loss of the GTRAP3-18 gene resulted in increased neuronal GSH content and neuroprotection against oxidative stress. Moreover, GTRAP3-18 KO mice performed better in motor/spatial learning and memory tests than wild-type mice. These results indicate that the suppression of GTRAP3-18 increases neuronal resistance to oxidative stress and also facilitates cognitive function by increasing GSH content. The present study may provide a molecular basis for the development of treatments for neurodegenerative diseases.