• 1 μM metformin enhanced the self-renewal and differentiation of NPCs.• Neuronal differentiation was dependent on AMPK/atypical PKC and cyclic AMP response element-binding protein (CREB or CBP).• Metformin mediated self-renewal and proliferation of NPCs via activation of Tap73 gene. The protein p73 is related to the tumor suppressor, p53.• Conclusion: Metformin enhances neurogenesis suggesting a role for metformin in neurodegenerative diseases. This evidence concerns the gene CREB1 and neurodegenerative disease.