| RRC ID |
51315
|
| Author |
Yoneyama T, Arai MA, Akamine R, Koryudzu K, Tsuchiya A, Sadhu SK, Ahmed F, Itoh M, Okamoto R, Ishibashi M.
|
| Title |
Notch Inhibitors from Calotropis gigantea That Induce Neuronal Differentiation of Neural Stem Cells.
|
| Journal |
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.
|
| Volume |
80(9)
|
| Pages |
2453-2461
|
| Published |
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
|
| Times Cited |
11
|
| Resource |
| DNA material |
pEF-BOSneo-mNotch1 RAMIC (RDB06771)
pGa981-6 (RDB06776). |
