To stop the progression of Alzheimer’s disease in the early stage, it is necessary to identify new therapeutic targets. We examined striatal-enriched phosphatase 61 expression in the brain tissues of 12-month-old APPswe/PSEN1dE9 transgenic mice. Immunohistochemistry showed that al-enriched phosphatase 61 protein expression was significantly increased but phosphorylated N-methyl-D-aspartate receptor 2B levels were significantly decreased in the cortex and hippocam-pus of APPswe/PSEN1dE9 transgenic mice. Western blotting of a cel model of Alzheimer’s disease consisting of amyloid-beta peptide (1-42)-treated C57BL/6 mouse cortical neurons in vitro showed that valeric acid (AP5), an N-methyl-D-aspartate receptor antagonist, significantly inhibited amyloid-beta 1-42-induced increased activity of striatal-enriched phosphatase 61. In addition, the phos-phorylation of N-methyl-D-aspartate receptor 2B at Tyr1472 was impaired in amyloid-beta 1-42-treated cortical neurons, but knockdown of striatal-enriched phosphatase 61 enhanced the phosphorylation of N-methyl-D-aspartate receptor 2B. Col ectively, these findings indicate that striatal-enriched phosphatase 61 can disturb N-methyl-D-aspartate receptor transport and inhibit the progression of learning and study disturbances induced by Alzheimer’s disease. Thus, al-enriched phosphatase 61 may represent a new target for inhibiting the progression of Alzheimer’s disease.

CaMKⅡ介导的谷氨酸受体磷酸化

钙/钙调蛋白依赖的蛋白激酶Ⅱ (Ca2+/calmodulin-dependent protein kinase Ⅱ,CaMKⅡ)在脑内兴奋性突触部位丰富表达.通过催化谷氨酸受体和众多突触蛋白磷酸化,CaMKⅡ调节磷酸化蛋白在基础或细胞兴奋时的转运、分布和功能.谷氨酸NMDA受体是CaMKⅡ的直接底物,有证据表明CaMKⅡ直接与NMDA受体胞内C末端相互结合,催化一特定丝氨酸(S1303)的磷酸化.CaMKⅡ也加强谷氨酸AMPA受体的磷酸化,通过磷酸化AMPA受体C末端特定的丝氨酸(S831),CaMKⅡ增强AMPA受体的功能.此外,CaMKⅡ可与代谢型谷氨酸受体mGluR1亚型的胞内C末端结合,促进一特定苏氨酸(T871)的磷酸化,从而促进受体兴奋后脱敏.CaMKⅡ在正常状态下与mGluR5受体结合以储存于突触内,刺激mGluR5受体时,CaMKⅡ与mGluR5受体分离,转运至NMDA受体,以介导mGluR5信号对NMDA受体的增强作用.总之,CaMKⅡ与谷氨酸受体相互作用,改变受体磷酸化水平,参与受体的数量和功能以及突触传导活动的调节.

七氟烷通过激活 GluN2B －ERK1／2信号通路抑制 ADDLs 神经毒性

目的：探讨七氟烷对 Aβ来源的扩散性配体（Aβ－derived diffusible ligands，ADDLs）神经毒性的影响，揭示七氟烷对阿尔茨海默病（Alzheimer disease， AD）损伤神经元的保护作用及其机制。方法体外培养2周的大鼠海马神经元随机分为4组：对照组、ADDLs 组、七氟烷组以及合用组。免疫印迹方法观察七氟烷及 ADDLs 对p －ERK1／2、NMDA 受体各亚基表达、GluN2B 亚基的第172位酪氨酸磷酸化水平的影响；细胞组分分离方法探索七氟烷及 ADDLs 影响 NMDA 受体各亚基在细胞膜表面表达的规律；细胞免疫荧光化学方法检测七氟烷及 AD－DLs 对 GluN2B 亚基在突触上表达水平的影响。结果1．5％七氟烷作用2 h可显著恢复 ADDLs 降低的 ERK1／2的活化水平；1．5％七氟烷处理2 h 可显著逆转 ADDLs 降低的 GluN1和 GluN2B 亚基在细胞膜表面表达的水平，但是对细胞膜表面 GluN2A 的表达水平无明显影响，对 NMDA 受体各亚基总的表达水平无影响；细胞免疫荧光化学结果显示七氟烷可以显著增加 ADDLs 降低的 GluN2B 亚基在突触上的表达量。结论七氟烷通过激活GluN2B －ERK1／2信号通路抑制 ADDLs 的神经毒性。