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Notch Inhibitors from Calotropis gigantea That Induce Neuronal Differentiation of Neural Stem Cells
Journal of Natural Products ( IF 3.3 ) Pub Date : 2017-08-17 00:00:00 , DOI: 10.1021/acs.jnatprod.7b00282 Tatsuro Yoneyama 1 , Midori A. Arai 1 , Ryuta Akamine 1 , Kazune Koryudzu 1 , Anna Tsuchiya 1 , Samir K. Sadhu 2 , Firoj Ahmed 3 , Motoyuki Itoh 1 , Ryuichi Okamoto 4 , Masami Ishibashi 1
Journal of Natural Products ( IF 3.3 ) Pub Date : 2017-08-17 00:00:00 , DOI: 10.1021/acs.jnatprod.7b00282 Tatsuro Yoneyama 1 , Midori A. Arai 1 , Ryuta Akamine 1 , Kazune Koryudzu 1 , Anna Tsuchiya 1 , Samir K. Sadhu 2 , Firoj Ahmed 3 , Motoyuki Itoh 1 , Ryuichi Okamoto 4 , Masami Ishibashi 1
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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 from Calotropis gigantea were identified as inhibitors of the Notch signaling pathway. Hes1 and Hes5 are target genes of the Notch signaling pathway, and compound 1, 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.
中文翻译：
来自Calotropis gigantea的Notch抑制剂可诱导神经干细胞的神经元分化
由于神经元的结构和功能丧失，发生诸如阿尔茨海默氏病和帕金森氏病的神经退行性疾病。为了潜在地治疗神经退行性疾病，神经干细胞（NSC）的神经元分化的加速器已被关注，并构建了一种基于细胞的测定系统，用于测量Notch信号通路的活性。使用该测定系统，从巨鳞Calotropis中分离出的八种化合物被鉴定为Notch信号通路的抑制剂。Hes1和Hes5是Notch信号通路的靶基因，化合物1（称为uscharin）降低了测定细胞和MEB5细胞（小鼠NSC）中Hes1和Hes5的蛋白质水平。此外，uscharin（1）增强了MEB5细胞向神经元的分化。uscharin（1）的Notch信号抑制活性的机制是加速MEB5细胞中Notch胞内域（NICD）的降解。
更新日期：2017-08-17
中文翻译：
来自Calotropis gigantea的Notch抑制剂可诱导神经干细胞的神经元分化
由于神经元的结构和功能丧失，发生诸如阿尔茨海默氏病和帕金森氏病的神经退行性疾病。为了潜在地治疗神经退行性疾病，神经干细胞（NSC）的神经元分化的加速器已被关注，并构建了一种基于细胞的测定系统，用于测量Notch信号通路的活性。使用该测定系统，从巨鳞Calotropis中分离出的八种化合物被鉴定为Notch信号通路的抑制剂。Hes1和Hes5是Notch信号通路的靶基因，化合物1（称为uscharin）降低了测定细胞和MEB5细胞（小鼠NSC）中Hes1和Hes5的蛋白质水平。此外，uscharin（1）增强了MEB5细胞向神经元的分化。uscharin（1）的Notch信号抑制活性的机制是加速MEB5细胞中Notch胞内域（NICD）的降解。
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