Galanthamine Promotes Neuronal Differentiation and Neurite Outgrowth of Neural Progenitor/Stem Cells by Up-Regulating IGF-2

Galanthamine, an alkaloid from the Amaryllidaceae family, serves as an inhibitor of acetylcholinesterase. Beause of its central cholinergic properties, galanthamine is currently being researched as a potential therapeutic agent for the treatment of Alzheimer's disease. Nevertheless, the full extent of its other biological activities is still unclear. Here, we investigated the therapeutic potential of galanthamine in inducing neuronal differentiation and enhancing neurite outgrowth in neural stem and progenitor cells (NSPCs). Our comprehensive analysis revealed significant alterations in neuronal morphology and complexity during neuronal maturation following galanthamine treatment. Specifically, galanthamine significantly increased the percentage of multiple-neurite neurons, suggesting its ability to stimulate neurite formation and promote the development of extensive neuronal networks. Additionally, treatment with galanthamine resulted in a considerable increase in the proportion of mature-appearing neurons, characterized by elongated and intricate dendrites, suggesting its potential in enhancing neural plasticity and repair. Importantly, we further confirmed that galanthamine promotes neuronal differentiation in NSPCs through up-regulation of the IGF2 signaling pathway. Altogether, these findings contribute significantly to our understanding of the effects of galanthamine on Alzheimer's disease and underscore its potential as a therapeutic agent for this neurodegenerative condition.