Acta pharmaceutica Sinica. B · 2026
Neuroprotection by YZG-331 in postoperative cognitive dysfunction via Mg2+-dependent blockade of NMDA receptors.
СтатьяНазвание и аннотация: Перевод в очереди
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Guo Han, Zhao Jiaojiao, Tian Keying, Guo Qinghui, Chen Siruan, Ge Yuhan, Guo Wenyan, Lin Xingchen, Bai Hui, Yang Lei, Yang Lei, Qin Xia, Zhang Panpan, Jia Zhanfeng, Zheng Ruifang, Yang Zuxiao, Shi Yun Stone, Kong Dezhi, Ji Tengfei, Zhang Wei
Аннотация
Postoperative cognitive dysfunction (POCD) is a debilitating neurological complication that occurs following surgery, for which no effective interventions are currently available. Here, we identified YZG-331, a novel adenosine analog, as a promising neuroprotective agent that rescues cognitive deficits and mitigates dendritic spine loss in a murine POCD model. Integrated proteomic profiling and bioinformatics pathway analysis revealed that YZG-331 selectively targets NMDA receptor (NMDAR) signaling. Electrophysiological recordings and living-cell calcium imaging demonstrated that YZG-331 suppressed NMDAR-mediated currents and calcium influx in a dose-dependent manner. Furthermore, Mg2+ is required for YZG-331 to inhibit NMDAR activity. YZG-331 disrupts the formation of NMDAR condensates in the presence of Mg2+, thereby attenuating NMDAR-mediated excitotoxicity. Our findings establish YZG-331 as a prospective therapeutic candidate for POCD and reveal Mg2+-dependent receptor modulation as a novel pharmacological strategy for targeting NMDAR-associated neuropathologies.