Prion protein attenuates excitotoxicity by inhibiting NMDA receptors.
Prion protein attenuates excitotoxicity by inhibiting NMDA receptors.
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prion蛋白通过抑制NMDA受体减轻兴奋性毒性。
DOI：
10.1083/jcb.200711002
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发表时间：
2008-05-05
影响因子：
7.8
通讯作者：
Zamponi, Gerald W.
中科院分区：
文献类型：
--
作者：
Khosravani, Houman;Zhang, Yunfeng;Tsutsui, Shigeki;Hameed, Shahid;Altier, Christophe;Hamid, Jawed;Chen, Lina;Villemaire, Michelle;Ali, Zenobia;Jirik, Frank R.;Zamponi, Gerald W.
它是公认的，错误折叠形式的细胞朊蛋白（PrP [PrPC]）的发生和发展的传染性海绵状脑炎是至关重要的，而本地PrPC的功能仍然不完全了解。为了确定PrPC的生理作用，我们研究了从PrP缺失小鼠中分离的海马神经元的神经生理学特性。我们发现，PrP-null小鼠神经元表现出增强和大幅延长的N-甲基-D-天冬氨酸（NMDA）诱发的电流作为一个功能上调的NMDA受体（NMDARs）含有NR 2D亚基的结果。这些影响是phenocopied的RNA干扰和抢救后，外源性PrPC的过度表达。增强的NMDAR活性导致体外和体内神经元兴奋性增加以及谷氨酸兴奋毒性增强。因此，天然PrPC通过其抑制NR 2D亚基的能力介导重要的神经保护作用。
It is well established that misfolded forms of cellular prion protein (PrP [PrPC]) are crucial in the genesis and progression of transmissible spongiform encephalitis, whereas the function of native PrPC remains incompletely understood. To determine the physiological role of PrPC, we examine the neurophysiological properties of hippocampal neurons isolated from PrP-null mice. We show that PrP-null mouse neurons exhibit enhanced and drastically prolonged N-methyl-d-aspartate (NMDA)–evoked currents as a result of a functional upregulation of NMDA receptors (NMDARs) containing NR2D subunits. These effects are phenocopied by RNA interference and are rescued upon the overexpression of exogenous PrPC. The enhanced NMDAR activity results in an increase in neuronal excitability as well as enhanced glutamate excitotoxicity both in vitro and in vivo. Thus, native PrPC mediates an important neuroprotective role by virtue of its ability to inhibit NR2D subunits.
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影响因子：
5.3
作者：
Herms, J;Tings, T;Kretzschmar, H
通讯作者：
Kretzschmar, H
影响因子：
25
作者：
Altier, C;Khosravani, H;Zamponi, GW
通讯作者：
Zamponi, GW
影响因子：
4.5
作者：
Carleton, A;Tremblay, P;Lledo, PM
通讯作者：
Lledo, PM
影响因子：
3.5
作者：
Khosravani, H;Altier, C;Colicos, MA
通讯作者：
Colicos, MA
影响因子：
2.9
作者：
Maglio, Laura E.;Martins, Vilma R.;Ramirez, Oscar A.
通讯作者：
Ramirez, Oscar A.