通过干扰N-甲基-D-天冬氨酸受体与突触后密度蛋白95的蛋白质相互作用来治疗缺血性脑损伤。
Treatment of ischemic brain damage by perturbing NMDA receptor- PSD-95 protein interactions.
作者信息
Aarts Michelle, Liu Yitao, Liu Lidong, Besshoh Shintaro, Arundine Mark, Gurd James W, Wang Yu-Tian, Salter Michael W, Tymianski Michael
机构信息
Toronto Western Hospital Research Institute, 11-416 MC-PAV, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada.
出版信息
Science. 2002 Oct 25;298(5594):846-50. doi: 10.1126/science.1072873.
N-methyl-D-aspartate receptors (NMDARs) mediate ischemic brain damage but also mediate essential neuronal excitation. To treat stroke without blocking NMDARs, we transduced neurons with peptides that disrupted the interaction of NMDARs with the postsynaptic density protein PSD-95. This procedure dissociated NMDARs from downstream neurotoxic signaling without blocking synaptic activity or calcium influx. The peptides, when applied either before or 1 hour after an insult, protected cultured neurons from excitotoxicity, reduced focal ischemic brain damage in rats, and improved their neurological function. This approach circumvents the negative consequences associated with blocking NMDARs and may constitute a practical stroke therapy.
N-甲基-D-天冬氨酸受体（NMDARs）介导缺血性脑损伤，但也介导神经元的基本兴奋。为了在不阻断NMDARs的情况下治疗中风，我们用能破坏NMDARs与突触后致密蛋白PSD-95相互作用的肽转导神经元。这一过程使NMDARs与下游神经毒性信号分离，而不阻断突触活动或钙内流。这些肽在损伤前或损伤后1小时应用时，可保护培养的神经元免受兴奋毒性，减少大鼠局灶性缺血性脑损伤，并改善其神经功能。这种方法规避了与阻断NMDARs相关的负面后果，可能构成一种实用的中风治疗方法。
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