Figure 1.

SIRT1 during neurogenesis. SIRT1 disruption alters the differentiation potential of neural progenitor cells (NPCs). Two different models have been proposed. (A) In NPCs under differentiation conditions, SIRT1 transiently translocates to the nucleus, where it interacts with N-CoR. The N-CoR/SIRT1 complex binds to the promoter region of the Hes1 gene, a downstream target of the Notch signaling pathway, promoting neuronal differentiation. (B) Differentiation potential of NPCs is affected by the redox status via SIRT1 activation. In a reducing environment, Hes1 recruits transcription activators such as CREB binding protein (CBP) to the Mash1 promoter, a key transcription factor during neuronal differentiation. Under oxidizing conditions, Hes1 recruits SIRT1 to the Mash1 promoter, inducing histone deacetylation. This represses the transcription of Mash1 and promotes astroglial differentiation.