Notch Inhibitors from Calotropis gigantea That Induce Neuronal Differentiation of Neural Stem Cells.
Tatsuro YoneyamaMidori A AraiRyuta AkamineKazune KoryudzuAnna TsuchiyaSamir K SadhuFiroj AhmedMotoyuki ItohRyuichi OkamotoMasami IshibashiPublished in: Journal of natural products (2017)
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.
Keyphrases
- induced apoptosis
- signaling pathway
- cell cycle arrest
- neural stem cells
- pi k akt
- cell proliferation
- endoplasmic reticulum stress
- oxidative stress
- epithelial mesenchymal transition
- cell death
- spinal cord injury
- genome wide
- cell therapy
- climate change
- mesenchymal stem cells
- wastewater treatment
- risk assessment
- human health
- reactive oxygen species
- replacement therapy