凝聚态Aβ 25～35可通过JNK/p38 MAPK途径诱导胎鼠皮层神经元Tau蛋白过度磷酸化

目的 探讨JNK/p38 MAPK在β淀粉样蛋白多肽片段25～35(Aβ25～35)诱导的阿尔茨海默病(AD)样胎鼠皮层神经元Tau蛋白过度磷酸化中的作用.方法 应用蛋白免疫印迹和免疫细胞化学染色的方法,观察Tau蛋白磷酸化和JNK/p38丝裂原活化的蛋白激酶(JNK/p38 MAPK)的表达情况.结果 凝聚态Aβ25～35(20μmol/L)作用于皮层神经元12h,Tau蛋白Ser396、Ser199/202、Thr205位点的磷酸化水平明显增高,同时JNK/p38 MAPK的总量及其活性形式-磷酸化JNK/p38 MAPK的蛋白表达水平也增加.结论 Aβ25～35可通过激活JNK/p38 MAPK使Tau蛋白的磷酸化水平增高.

BETA AMYLOID PEPTIDE 25-35 INDUCES Tau PROTEIN HYPERPHOSPHORYLATION IN CORTICAL NEURONS THROUGH JNK/p38 MAPK PATH IN RAT EMBRYO

Objective To investigate the effect and the molecular mechanism of aggregated beta-amyloid peptide 25-35 (Aβ SUB>25-35/SUB>) on the level of Tau protein phosphorylation in rat embryo cortical neurons. Methods Western blotting and immunocytochemical stain were performed to observe the Tau protein phosphorylation and the expression of JNK/p38 MAPK Results The level of Tau protein phosphorylation in the sites of SerSUP>396/SUP>, SerSUP> 199/202/SUP> and ThrSUP>205/SUP> increased after Aβ SUB>25-35/SUB> of 20μmol/L was exposed to cortical neurons, meanwhile the level of JNK/p38 MAPK also increased after treatment with Aβ25-35 for 12 hours. Pretreatment with specific inhibitor of JNK/p38 MAPK markedly attenuated Tau pr