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首页> 外文期刊>Journal of Ginseng Research >20(S)-protopanaxadiol promotes the migration, proliferation, and differentiation of neural stem cells by targeting GSK-3β in the Wnt/GSK-3β/β-catenin pathway
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20(S)-protopanaxadiol promotes the migration, proliferation, and differentiation of neural stem cells by targeting GSK-3β in the Wnt/GSK-3β/β-catenin pathway

机译：20（S） - 通过在Wnt / GSK-3β/β-catenin途径中靶向GSK-3β，促进神经干细胞的迁移，增殖和分化促进神经干细胞的迁移，增殖和分化

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Background Active natural ingredients, especially small molecules, have recently received wide attention as modifiers used to treat neurodegenerative disease by promoting neurogenic regeneration of neural stem cell (NSC) in situ . 20(S)-protopanaxadiol (PPD), one of the bioactive ingredients in ginseng, possesses neuroprotective properties. However, the effect of PPD on NSC proliferation and differentiation and its mechanism of action are incompletely understood. Methods In this study, we investigated the impact of PPD on NSC proliferation and neuronal lineage differentiation through activation of the Wnt/glycogen synthase kinase (GSK)-3β/β-catenin pathway. NSC migration and proliferation were investigated by neurosphere assay, Cell Counting Kit-8 assay, and EdU assay. NSC differentiation was analyzed by Western blot and immunofluorescence staining. Involvement of the Wnt/GSK3β/β-catenin pathway was examined by molecular simulation and Western blot?and verified using gene transfection. Results PPD significantly promoted neural migration and induced a significant increase in NSC?proliferation in a time- and dose-dependent manner. Furthermore, a remarkable increase in antimicrotubule-associated protein 2 expression and decrease in nestin protein expression were induced by PPD. During the differentiation process, PPD targeted and stimulated the phosphorylation of GSK-3β at Ser9 and the active forms of β-catenin, resulting in activation of the Wnt/GSK-3β/β-catenin pathway. Transfection of NSCs with a constitutively active GSK-3β mutant at S9A significantly hampered the proliferation and neural differentiation mediated by PPD. Conclusion PPD promotes NSC proliferation and neural differentiation in?vitro via activation of the Wnt/GSK-3β/β-catenin pathway by targeting GSK-3β, potentially having great significance for the treatment of neurodegenerative diseases.
机译：背景技术通过以原位促进神经干细胞（NSC）的神经源性再生来治疗神经变性疾病的改性剂，最近，活性天然成分最近受到了广泛的关注。 20（s） - 人参中生物活性成分之一的 - 促丙二醇（PPD）具有神经保护性。然而，PPD对NSC增殖和分化的影响及其作用机制是不完全理解的。方法在本研究中，通过激活Wnt /糖原合酶激酶（GSK）-3β/β-catenin途径，研究了PPD对PPD对NSC增殖和神经元谱系分化的影响。通过神经圈测定，细胞计数试剂盒-8测定和EDU测定来研究NSC迁移和增殖。通过蛋白质印迹和免疫荧光染色分析NSC分化。通过分子模拟和Western印迹检查Wnt / GSK3 /β-Catenin途径的涉及α，并使用基因转染进行验证。结果PPD显着促进了神经迁移，并以时序和剂量依赖的方式诱导了NSC的显着增加。此外，PPD诱导了抗微生多药物相关蛋白2表达和巢蛋白蛋白表达减少的显着增加。在分化过程中，PPD靶向并刺激SER9的GSK-3β的磷酸化和β-连环蛋白的活性形式，导致WNT / GSK-3β/β-连环蛋白途径的活化。在S9a下用组成型活性GSK-3β突变体转染NSCs显着阻碍了PPD介导的增殖和神经分化。结论PPD通过靶向GSK-3β，通过激活WNT / GSK-3β/β-Catenin途径促进NSC增殖和神经分化。潜在地​​对治疗神经变性疾病具有重要意义。

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