The DREAM Protein Negatively Regulates the NMDA Receptor through Interaction with the NR1 Subunit

• DOI: 10.1523/jneurosci.1312-10.2010
• Publication Date: 2010-06-02T17:28:08Z
• Authors: Ying Zhang; Ping Su; Ping Liang; Tao Liu; Xu Liu; Xin-Ying Liu; Bo Zhang; Tao Han; Yan-Bing Zhu; Dong-Min Yin; Junfa Li; Zhuan Zhou; Ke-Wei Wang; Yun Wang
• Keywords: Excitotoxicity

Glutamate-induced excitotoxicity has been implicated in the etiology of stroke, epilepsy, and neurodegenerative diseases. NMDA receptors (NMDARs) play a pivotal role excitotoxic injury; however, clinical trials testing NMDAR antagonists as neuroprotectants have discouraging. The development novel neuroprotectant molecules is being vigorously pursued. Here, we report that downstream regulatory element antagonist modulator (DREAM) significantly inhibits surface expression NMDARs NMDAR-mediated current. Overexpression DREAM showed neuroprotection against neuronal injury, whereas knockdown enhanced NMDA-induced toxicity. could directly bind to C0 domain NR1 subunit. Although contains multiple binding sites for subunit, residues 21-40 N terminus are main site Thus, might relieve autoinhibition conferred by 1-50 derepress core competitive mechanism. Intriguingly, cell-permeable TAT-21-40 peptide, constructed according critical currents primary cultured hippocampal neurons neuroprotective effect on vitro injury vivo ischemic brain damage. Moreover, both pretreatment posttreatment effective excitotoxicity. In summary, this work reveals novel, negative regulator provides an attractive candidate treatment excitotoxicity-related disease.