Notch Inhibitors from Calotropis gigantea That Induce Neuronal Differentiation of Neural Stem Cells
Notch Inhibitors from Calotropis gigantea That Induce Neuronal Differentiation of Neural Stem Cells
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来自牛角瓜的 Notch 抑制剂可诱导神经干细胞的神经元分化
DOI：
10.1021/acs.jnatprod.7b00282
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发表时间：
2017
影响因子：
5.1
通讯作者：
Ishibashi Masami
中科院分区：
文献类型：
--
作者：
Yoneyama Tatsuro;Arai Midori A.;Akamine Ryuta;Koryudzu Kazune;Tsuchiya Anna;Sadhu Samir K.;Ahmed Firoj;Itoh Motoyuki;Okamoto Ryuichi;Ishibashi Masami
神经退行性疾病如阿尔茨海默病和帕金森病的发生是由于神经元的结构和功能的丧失。为了治疗神经退行性疾病，神经干细胞（NSCs）的神经元分化的加速剂已被关注，并构建了用于测量Notch信号通路活性的基于细胞的测定系统。利用该系统，从马蹄莲中分离得到8个化合物，其中Hes1和Hes5是Notch信号通路的靶基因，化合物1（uscharin）能降低Notch信号通路靶基因Hes1和Hes5在被测细胞和MEB 5细胞（小鼠神经干细胞）中的蛋白水平。此外，uscharin（1）促进MEB 5细胞向神经元的分化。Ucharin（1）抑制Notch信号传导的机制可能是加速MEB 5细胞中Notch胞内结构域（NICD）的降解。
Neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease occur due to loss of the structure and function of neurons. For the potential treatment of neurodegenerative diseases, accelerators of neuronal differentiation of neural stem cells (NSCs) have been focused on and a cell-based assay system for measuring Notch signaling pathway activity was constructed. Using this assay system, eight compounds isolated fromCalotropis giganteawere identified as inhibitors of the Notch signaling pathway.Hes1andHes5are target genes of the Notch signaling pathway, and compound1, called uscharin, decreased the protein levels of Hes1 and Hes5 in assay cells and MEB5 cells (mouse NSCs). Furthermore, uscharin (1) enhanced the differentiation of MEB5 cells into neurons. The mechanism of uscharin (1) for the Notch signaling inhibitory activity would be acceleration of the degradation of the Notch intracellular domain (NICD) in the MEB5 cells.