Abstract：
Alzheimer\'s disease is characterized by abnormal β-amyloid and tau accumulation, mitochondrial dysfunction, oxidative stress, and synaptic dysfunction. Here, we aimed to assess the mechanisms and signalling pathways in the neuroprotective effect of gastrodin, a phenolic glycoside, on murine neuroblastoma N2a cells expressing human Swedish mutant APP (N2a/APP). We found that gastrodin increased the levels of presynaptic-SNAP, synaptophysin, and postsynaptic-PSD95 and reduced phospho-tau Ser396, APP and Aβ1-42 levels in N2a/APP cells. Gastrodin treatment reduced reactive oxygen species generation, lipid peroxidation, mitochondrial fragmentation and DNA oxidation; restored mitochondrial membrane potential and intracellular ATP production. Upregulated phospho-GSK-3β and reduced phospho-ERK and phospho-JNK were involved in the protective effect of gastrodin. In conclusion, we demonstrated the neuroprotective effect of gastrodin in the N2a/APP cell line by ameliorating the impairment on synaptic and mitochondrial function, reducing tau phosphorylation, Aβ1-42 levels as well as reactive oxygen species generation. These results provide new mechanistic insights into the potential effect of gastrodin in the treatment of Alzheimer\'s disease.
摘要：
阿尔茨海默病的特征是异常的β-淀粉样蛋白和tau积累，线粒体功能障碍，氧化应激，和突触功能障碍.这里,我们旨在评估天麻素神经保护作用的机制和信号通路，一种酚类糖苷，在表达人瑞典突变体APP(N2a/APP)的鼠神经母细胞瘤N2a细胞上。我们发现天麻素增加了突触前SNAP的水平，突触素,和突触后PSD95，并降低了N2a/APP细胞中磷酸化tauSer396，APP和Aβ1-42的水平。天麻素处理减少了活性氧的产生，脂质过氧化，线粒体片段化和DNA氧化；恢复线粒体膜电位和细胞内ATP产生。上调的磷酸-GSK-3β和减少的磷酸-ERK和磷酸-JNK参与天麻素的保护作用。总之,我们证明了天麻素在N2a/APP细胞系中的神经保护作用，通过改善突触和线粒体功能的损害，减少tau磷酸化，Aβ1-42水平以及活性氧的产生。这些结果为天麻素治疗阿尔茨海默病的潜在作用提供了新的机制见解。
