MiR-124-3p attenuates hyperphosphorylation of Tau protein-induced apoptosis via caveolin-1-PI3K/Akt/GSK3β pathway in N2a/APP695swe cells.
MiR-124-3p attenuates hyperphosphorylation of Tau protein-induced apoptosis via caveolin-1-PI3K/Akt/GSK3β pathway in N2a/APP695swe cells.
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DOI：
10.18632/oncotarget.15149
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发表时间：
2017-04-11
期刊：
影响因子：
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通讯作者：
Li Y
中科院分区：
文献类型：
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作者：
Kang Q;Xiang Y;Li D;Liang J;Zhang X;Zhou F;Qiao M;Nie Y;He Y;Cheng J;Dai Y;Li Y
Tau过度磷酸化形成神经原纤维缠结被认为是阿尔茨海默病(AD)发病机制中的一个重要事件。MiR-124-3p属于microRNA(MiRNA)家族，在AD中表达显著降低，但miR-124-3p在AD发病机制中的作用尚不清楚。我们观察到miR-124-3p在N2a/APP695swe细胞中的表达显著降低，并且在不改变总Tau蛋白的情况下，模拟miR-124-3p不仅抑制了细胞的凋亡和Tau蛋白的异常过度磷酸化，而且还上调了N2a/APP695swe细胞中小泡蛋白1、磷脂酰肌醇3-激酶(PI3K)、磷酸化Akt(Akt-Ser473)/Akt、磷酸糖原合成酶-3β(GSK-3β-Ser9)/GSK-3β的表达水平。我们进一步发现miR-12-3p直接靶向小窝蛋白-1；miR-124-3p通过调节小窝蛋白-1-PI3K/Akt/GSK3β通路抑制AD时Tau的异常过度磷酸化。本研究揭示miR-124-3p在AD中可能具有神经保护作用，可能为AD的治疗提供新的思路和靶点。
Hyperphosphorylation of Tau forming neurofibrillary tangles has been considered as a crucial event in the pathogenesis of Alzheimer's disease (AD). MiR-124-3p belongs to microRNA (miRNA) family and was markedly decreased in AD, however, the functions of miR-124-3p in the pathogenesis of AD remain unknown. We observed that the expression of miR-124-3p was significantly decreased in N2a/APP695swe cells; and transfection of miR-124-3p mimics not only attenuated cell apoptosis and abnormal hyperphosphorylation of Tau protein without any changes of total Tau protein, but also increased expression levels of Caveolin-1, phosphoinositide 3-kinase (PI3K), phospho-Akt (Akt-Ser473)/Akt, phospho-glycogen synthase kinase-3 beta (GSK-3β-Ser9)/GSK-3β in N2a/APP695swe cells. We further found that miR-12-3p directly targeted Caveolin-1; miR-124-3p inhibited abnormal hyperphosphorylation of Tau by regulating Caveolin-1-PI3K/Akt/GSK3β pathway in AD. This study reveals that miR-124-3p may play a neuroprotective role in AD, which may provide new ideas and therapeutic targets for AD.