The transdifferentiation of human mesenchymal stem cells (hMSC) to functional neurons is crucial for the development of future neuro-regenerative therapeutics. Currently, transdifferentiation of hMSCs to neurons requires a "" along with neural growth factors. The role of the individual molecules present in a "chemical cocktail" is poorly understood and may cause unwanted toxicity or adverse effects. Toward, this goal, we have showcased the discovery of an imidazole-based "single-molecule" transdifferentiation initiator SG-145C. This discovery was achieved screening of a small molecule library through extensive studies to shortlist the best-fitting molecules. This discovery evolved through a careful selection to target Glycogen synthase kinase-3β (GSK-3β), which is one of the important proteins responsible for neurogenesis. Rigorous computational experiments, as well as extensive biological assays, confirmed that SG-145C has significant potential to transdifferentiate hMSCs to neurons. Interestingly, our results suggest that SG-145C can inhibit the proteasomal degradation of phosphorylated β-catenin, in turn promoting transdifferentiation of hMSCs into neurons the Wnt pathway.
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| http://dx.doi.org/10.3389/fnmol.2022.1002419 | DOI Listing |
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