Introduction: Alpha-Lipoic Acid (ALA) is known for its antioxidant and antiinflammatory properties; however, its direct role in neurogenesis remains undefined. This study evaluated the neurogenic potential of the R-enantiomer (R-ALA) using transcriptomic profiling and in vitro validation. Methods: Transcriptome analysis of R-ALA-treated cells was performed to identify differentially expressed genes and enriched pathways. Validation was conducted in different cell lines (C6, PC12, TGW) to assess neurite morphology and neuronal marker expression. Results: R-ALA induced strong upregulation of several neurogenesis-associated biomarkers and enriched pathways related to neurogenesis, axonogenesis, dendritogenesis, gliogenesis, and neurotransmission (serotonergic, GABAergic). In line with transcriptomic predictions, treated cells exhibited neurite outgrowth and increased expression of neuronal markers, including MAP2, β- tubulin III, NF-200, and GAP43. Discussion: The upregulation of neuron-specific markers and downregulation of progenitorassociated CD44 suggest a comprehensive activation of neuroplastic and regenerative processes, reinforcing ALA’s potential as a neurogenic agent. Conclusion: These findings provide the first integrated transcriptome-to-phenotype evidence that R-ALA promotes neurogenesis and neuronal differentiation in vitro, offering a basis for further in vivo exploration in neurodegenerative disorders.
Gupta et al. (Mon,) studied this question.