Wang, H.-H. | Search bioRxiv

bioRxiv2024

Neuroprotective Effects of Bioactive Molecules Derived from Tobacco as Potential Therapeutic Candidates for Alzheimer Disease

Neurodegenerative diseases are significant global health challenges, particularly with an aging population. While tobacco is traditionally linked to health risks, recent studies suggest it may contain compounds beneficial for neurodegenerative conditions. Herein, we explore the potential of bioactive compounds in tobacco as neuroprotective agents for Alzheimers disease (AD). Using genetic engineering, we developed a novel approach with neural progenitor cells (NPCs) derived from embryonic stem cells, equipped with an NF-{kappa}B reporter system to screen tobacco extracts. Our screenings identified three compounds with significant inhibitory effects on NF-{kappa}B activation, a key mediator of neuroinflammation in AD. Among these, rutin exhibited profound neuroprotective effects in an NPC damage model induced by Amyloid-{beta}25-35, reducing apoptotic cell death, enhancing cellular proliferation, and activating critical survival signaling pathways. This modulation underlies rutins anti-inflammatory and neuroprotective activities. Together, our findings support the potential of tobacco-derived compounds in AD therapy and lay the foundation for further exploration of their pharmaceutical value.

pharmacology and toxicology↗

bioRxiv2023

Development of Synthetic Modulator Enabling Long-Term Propagation and Neurogenesis of Human-Derived Neural Progenitor Cells

Neural progenitor cells (NPCs) are important cells for in vitro drug screening and the cell-based therapy for brain-related disorders, which requires well-defined and reproducible culture systems. Current strategy the use of protein growth factors presents challenges in terms of reproducibility and cost. In this study, we have developed a novel DNA-based modulator to regulate FGFR signaling of NPCs, enabling maintenance of the stemness over 50 passages and neurogenesis towards neurons. The DNA-based FGFR-agonist effectively promoted FGFR1 phosphorylation and activated the downstream ERK signaling pathway in FGFR1-positive cells. Using human embryonic stem cell lines, we differentiated them into NPCs and replaced basic fibroblast growth factor (bFGF) in the regulator culture medium with DNA-based FGFR-agonist for artificially elicited FGFR signaling. The results demonstrated that the FGFR-agonist could promote NPCs proliferation and neurosphere formation, recapitulating the function of bFGF. Notably, transcriptomic analysis revealed that FGFR-agonist could customize the stemness-associated transcription program, while decouples the neuronal differentiation program, highly resembling that the native ligand, bFGF. Moreover, our culture condition facilitated the successful propagation of NPCs for over 50 passages, while retaining their ability to efficiently differentiate into neurons. Overall, our approach provides a highly effective method for expanding NPCs, offering new opportunities for disease-in-dish research and drug screening for neural degeneration.

neuroscience↗