PSD-93 deletion inhibits Fyn-mediated phosphorylation of NR2B and protects against focal cerebral ischemia
PSD-93 deletion inhibits Fyn-mediated phosphorylation of NR2B and protects against focal cerebral ischemia
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PSD-93 缺失抑制 Fyn 介导的 NR2B 磷酸化并预防局灶性脑缺血
DOI：
10.1016/j.nbd.2014.04.010
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发表时间：
2014-08
影响因子：
6.1
通讯作者：
Xu Yun
中科院分区：
文献类型：
--
作者：
Zhang Meijuan;Li Qingjie;Chen Ling;Li Jie;Zhang Xin;Chen Xiang;Zhang Qingxiu;Shao Yuan;Xu Yun
修饰N-甲基-d-天冬氨酸受体（NMDAR）介导的兴奋毒性似乎是治疗缺血性卒中的潜在靶点。突触后密度蛋白-93（PSD-93）特异性结合NMDAR的C末端尾部，这对于将NMDAR活性偶联至特异性细胞内信号传导是至关重要的。本研究旨在探讨PSD-93基因敲除对成年小鼠局灶性脑缺血性中风模型是否具有神经保护作用，并探讨其可能的机制。PSD-93缺失也减少了由葡萄糖和氧剥夺（OGD）引起的培养的皮层神经元死亡。在用AP-5（NMDAR抑制剂）或PP 2（Src家族抑制剂）预处理的PSD-93 KO组和野生型（WT）组中不能诱导缺血长时程增强（i-LTP）。PSD-93 KO可降低MCAO后NR 2B在Tyr 1472的磷酸化以及NR 2B与Fyn之间的相互作用。总之，我们的研究表明，PSD-93 KO赋予针对缺血性脑损伤的深刻的神经保护作用，这可能与PSD-93缺失引起的对Fyn介导的NR 2B磷酸化的抑制作用有关。这些发现可能为缺血性脑卒中的治疗提供新的途径。
Modification ofN-methyl-d-aspartate receptor (NMDAR)-mediated excitotoxicity appears to be a potential target in the treatment of ischemic stroke. Postsynaptic density protein-93 (PSD-93) specifically binds the C-terminal tails of the NMDAR, which is critical to couple NMDAR activity to specific intracellular signaling. This study is to investigate whether PSD-93 disruption displays neuroprotection in a focal ischemic stroke model of adult mice and, if it does, to explore possible mechanisms.It was found that, following middle cerebral artery occlusion (MCAO), PSD-93 knockout (KO) mice manifested significant reductions in infarcted volume, neurological deficits and number of degenerated neurons. PSD-93 deletion also reduced cultured cortical neuronal death caused by glucose and oxygen deprivation (OGD). Ischemic long term potentiation (i-LTP) could not be induced in the PSD-93 KO group and wild type (WT) groups pretreated with either AP-5 (NMDAR inhibitor) or PP2 (Src family inhibitor). PSD-93 KO decreased the phosphorylation of the NR2B at Tyr1472 and the interaction between NR2B and Fyn after MCAO. Together, our study demonstrated that PSD-93 KO confers profound neuroprotection against ischemic brain injury, which probably links to the inhibitory effect on Fyn-mediated phosphorylation of NR2B caused by PSD-93 deletion. These findings may provide a novel avenue for the treatment of ischemic stroke.
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影响因子：
3.9
作者：
Hardingham GE
通讯作者：
Hardingham GE
DOI：
10.1523/jneurosci.23-17-06703.2003
发表时间：
2003-07
期刊：
The Journal of Neuroscience
影响因子：
--
作者：
Y. Tao;Gavin Rumbaugh;Guodu Wang;R. Petralia;Chengshui Zhao;F. Kauer;F. Tao;M. Zhuo;R. Wenthold-R.-Went
通讯作者：
Y. Tao;Gavin Rumbaugh;Guodu Wang;R. Petralia;Chengshui Zhao;F. Kauer;F. Tao;M. Zhuo;R. Wenthold-R.-Went
DOI：
10.1523/jneurosci.16-23-07407.1996
发表时间：
1996-12
期刊：
The Journal of Neuroscience
影响因子：
--
作者：
J. Brenman;K. S. Christopherson;S. E. Craven;Aaron W. McGee;D. Bredt
通讯作者：
J. Brenman;K. S. Christopherson;S. E. Craven;Aaron W. McGee;D. Bredt
DOI：
10.1073/pnas.96.2.435
发表时间：
1999-01-19
影响因子：
11.1
作者：
Tezuka, T;Umemori, H;Yamamoto, T
通讯作者：
Yamamoto, T
DOI：
10.1107/s1744309109043267
发表时间：
2009-12-01
影响因子：
0.9
作者：
Fiorentini, Monica;Nielsen, Ann Kallehauge;Gajhede, Michael
通讯作者：
Gajhede, Michael