Presentation Information
[1Chemi-14]Effects of Withanone and Cucurbitacin B combination on ER stress responses in human neuronal models
○Myat Nyein Khine1, Kazumi Hirano1, Sunil Kaul1, Renu Wadhwa1 (1. National Institute of Advanced Industrial Science and Technology (Japan))
Keywords:
Natural products,ER stress,Human neuronal models
[Purpose]
Endoplasmic reticulum (ER) stress is closely associated with neuronal dysfunction and neurodegenerative processes, and neurons are particularly sensitive to disturbances in protein homeostasis (Wolzak et al., 2022). Withanone and Cucurbitacin B are steroidal natural compounds reported to affect cellular stress-related pathways, and their combination has shown stress-modulating effects in non-neuronal cellular models (Garg et al., 2018). Because neuronal ER stress is directly linked to neurodegenerative pathology and Withanone has reported neuroprotective activity, this study aimed to examine the effects of their combination on ER stress responses in human neural stem cell-derived neuronal models.
[Method]
Human neural stem cell-derived neurons were exposed to tunicamycin to induce ER stress. Cells were treated with the combination of Withanone and Cucurbitacin B, and ER stress responses were evaluated by expression analysis of unfolded protein response-related markers, together with neuronal viability and phenotype-associated markers. In addition, alkyne-tagged analogs of both compounds were prepared as chemical probes for future mechanistic and localization studies.
[Results]
The combination treatment modulated tunicamycin-induced ER stress responses in human neuronal cells. Changes were observed in unfolded protein response-related marker expression, indicating that the compound combination influences stress-associated signaling pathways under neuronal ER stress conditions.
[Consideration]
These findings suggest that the combination of Withanone and Cucurbitacin B affects ER stress signaling in human neurons. The observed modulation of stress-related markers may be related to changes in neuronal cellular condition and phenotype under ER stress.[Conclusion]
This study provides a basic evaluation of a steroidal natural product combination as a modulator of ER stress responses in human neuronal models and establishes a basis for future chemical probe-based mechanistic analysis.
Endoplasmic reticulum (ER) stress is closely associated with neuronal dysfunction and neurodegenerative processes, and neurons are particularly sensitive to disturbances in protein homeostasis (Wolzak et al., 2022). Withanone and Cucurbitacin B are steroidal natural compounds reported to affect cellular stress-related pathways, and their combination has shown stress-modulating effects in non-neuronal cellular models (Garg et al., 2018). Because neuronal ER stress is directly linked to neurodegenerative pathology and Withanone has reported neuroprotective activity, this study aimed to examine the effects of their combination on ER stress responses in human neural stem cell-derived neuronal models.
[Method]
Human neural stem cell-derived neurons were exposed to tunicamycin to induce ER stress. Cells were treated with the combination of Withanone and Cucurbitacin B, and ER stress responses were evaluated by expression analysis of unfolded protein response-related markers, together with neuronal viability and phenotype-associated markers. In addition, alkyne-tagged analogs of both compounds were prepared as chemical probes for future mechanistic and localization studies.
[Results]
The combination treatment modulated tunicamycin-induced ER stress responses in human neuronal cells. Changes were observed in unfolded protein response-related marker expression, indicating that the compound combination influences stress-associated signaling pathways under neuronal ER stress conditions.
[Consideration]
These findings suggest that the combination of Withanone and Cucurbitacin B affects ER stress signaling in human neurons. The observed modulation of stress-related markers may be related to changes in neuronal cellular condition and phenotype under ER stress.[Conclusion]
This study provides a basic evaluation of a steroidal natural product combination as a modulator of ER stress responses in human neuronal models and establishes a basis for future chemical probe-based mechanistic analysis.
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