| First Author | Yin A | Year | 2020 |
| Journal | Transl Stroke Res | Volume | 11 |
| Issue | 2 | Pages | 214-227 |
| PubMed ID | 31250377 | Mgi Jnum | J:313180 |
| Mgi Id | MGI:6791524 | Doi | 10.1007/s12975-019-00708-9 |
| Citation | Yin A, et al. (2020) NDRG2 Protects the Brain from Excitotoxicity by Facilitating Interstitial Glutamate Uptake. Transl Stroke Res 11(2):214-227 |
| abstractText | Glutamate is a prominent neurotransmitter responsible for excitatory synaptic transmission and is taken up by sodium-dependent excitatory amino acid transporters (EAATs) on astrocytes to maintain synaptic homeostasis. Here, we report that N-myc downstream regulated gene 2 (NDRG2), a known tumor suppressor, is required to facilitate astroglial glutamate uptake and protect the brain from glutamate excitotoxicity after ischemia. NDRG2 knockout (Ndrg2(-/-)) mice exhibited an increase in cerebral interstitial glutamate and a reduction in glutamate uptake into astrocytes. The ability of NDRG2 to control EAAT-mediated glutamate uptake into astrocytes required NDRG2 to interact with and promote the function of Na(+)/K(+)-ATPase beta1, which could be disrupted by a Na(+)/K(+)-ATPase beta1 peptide. The deletion of NDRG2 or treatment with the Na(+)/K(+)-ATPase beta1 peptide significantly increased neuronal death upon a glutamate challenge and aggravated brain damage after ischemia. Our findings demonstrate that NDRG2 plays a pivotal role in promoting astroglial glutamate uptake from the interstitial space and protecting the brain from glutamate excitotoxicity. |
