神经发生
Wnt信号通路
神经保护
线粒体分裂
细胞生物学
信号转导
海马结构
下调和上调
齿状回
生物
化学
神经科学
线粒体
生物化学
基因
作者
Honghe Xiao,Jicong Chen,He Li,Ruihai Li,Haibo Wang,Hui‐Peng Song,Guo-Shun Shan,Tian Yu,Yu-Meng Zhao,Jin-ming Tian,Jingxian Yang
摘要
Restoring the compromised neurogenesis has been served as a potential strategy to rescue cognitive dysfunction of Alzheimer's disease (AD). In this study, we explored whether icarisid II (ICS II), a natural product possessing powerful neuroprotection, could recover the neurogenesis dysfunction of APP/PS1 mice, and investigated its underlying mechanisms. Our results showed that oral administration of ICS II could alleviate cognitive injuries of APP/PS1 mice, promote hippocampal neurogenesis, as well as stimulate Wnt/β-catenin signal pathway confirmed by upregulated Wnt-3a, phosphorylated glycogen synthase kinase-3β (p-GSK-3β), and β-catenin. ICS II also depressed mitochondrial fission evidenced by upregulated Mitofusin 1 (Mfn 1) and Mitofusin 2 (Mfn 2), and downregulated mitochondrial fission 1 protein (Fis 1), mitochondrial fission factor (Mff), and phosphorylated dynamin-related protein 1 (p-Drp 1). However, these effects of ICS II were blunted by XAV-939, an inhibitor of Wnt/β-catenin signaling pathway. In summary, our findings revealed that ICS II could improve neurogenesis and inhibit mitochondrial fission via activation of the Wnt/β-catenin signaling pathway, which contributed to cognitive function restoration of APP/PS1 mice. This study discovered a novel mechanism involving neurogenesis regulation underlying the therapeutic effects of ICS II against AD.
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