RRC ID 51315
著者 Yoneyama T, Arai MA, Akamine R, Koryudzu K, Tsuchiya A, Sadhu SK, Ahmed F, Itoh M, Okamoto R, Ishibashi M.
タイトル Notch Inhibitors from Calotropis gigantea That Induce Neuronal Differentiation of Neural Stem Cells.
ジャーナル J Nat Prod
Abstract 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.
巻・号 80(9)
ページ 2453-2461
公開日 2017-9-22
DOI 10.1021/acs.jnatprod.7b00282
PMID 28817274
MeSH Animals Calotropis / chemistry* Cell Differentiation / physiology* Cell Line Humans Mice Molecular Structure Neural Stem Cells / cytology* Neural Stem Cells / metabolism Neurons / chemistry Neurons / metabolism* Signal Transduction / drug effects* Signal Transduction / physiology
IF 3.885
引用数 11
リソース情報
遺伝子材料 pEF-BOSneo-mNotch1 RAMIC (RDB06771) pGa981-6 (RDB06776).