| First Author | Aoyama K | Year | 2012 |
| Journal | Neurobiol Dis | Volume | 45 |
| Issue | 3 | Pages | 973-82 |
| PubMed ID | 22210510 | Mgi Jnum | J:182338 |
| Mgi Id | MGI:5315235 | Doi | 10.1016/j.nbd.2011.12.016 |
| Citation | Aoyama K, et al. (2012) Increased neuronal glutathione and neuroprotection in GTRAP3-18-deficient mice. Neurobiol Dis 45(3):973-82 |
| abstractText | Glutathione (GSH) is an important neuroprotective molecule in the brain. The strategy to increase neuronal GSH level is a promising approach to the treatment of neurodegenerative diseases. However, the regulatory mechanism by which neuron-specific GSH synthesis is facilitated remains elusive. Glutamate transporter-associated protein 3-18 (GTRAP3-18) is an endoplasmic reticulum protein interacting with excitatory amino acid carrier 1 (EAAC1), which is a neuronal glutamate/cysteine transporter. To investigate the potential regulatory mechanism to increase neuronal GSH level in vivo, we generated GTRAP3-18-deficient (GTRAP3-18(-/-)) mice using a gene-targeting approach. Disruption of the GTRAP3-18 gene resulted in increased EAAC1 expression in the plasma membrane, increased neuronal GSH content and neuroprotection against oxidative stress. In addition, GTRAP3-18(-/-) mice performed better in motor/spatial learning and memory tests than wild-type mice. Therefore, the suppression of GTRAP3-18 increases neuronal resistance to oxidative stress by increasing GSH content and also facilitates cognitive function. The present results may provide a molecular basis for the development of treatments for neurodegenerative diseases. |
