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

谷胱甘肽（GSH）在大脑中起着重要的神经保护作用。提高大脑神经元谷胱甘肽水平的策略是治疗神经退行性疾病的一种很有前途的方法。为了研究体内增加神经元GSH水平的潜在调控机制，我们使用基因靶向方法培养了GTRAP3-18缺陷（GTRAP3-18 KO）小鼠。GTRAP3-18基因的缺失导致神经元GSH含量增加和抗氧化应激的神经保护作用。此外，GTRAP3-18 KO小鼠在运动/空间学习和记忆测试中表现优于野生型小鼠。这些结果表明，抑制GTRAP3-18可以增强神经元对氧化应激的抵抗力，并通过增加GSH含量促进认知功能。本研究可为神经退行性疾病的治疗提供分子基础。

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.