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Comment
. 2008 Apr;10(4):373-4.
doi: 10.1038/ncb0408-373.

Neurogenesis directed by Sirt1

Sergiy Libert  1 , Dena Cohen, Leonard Guarente
Affiliations
Comment

Neurogenesis directed by Sirt1

Sergiy Libert et al. Nat Cell Biol. 2008 Apr.

Abstract

Differentiation of neuronal stem cells into astrocytes or neurons is important in maintaining brain function. Oxidative stress and inflammation are now shown to bias differentiation toward astrocytes by modulating activity of the anti-ageing gene Sirt1. These findings link a longevity gene to the activity of neuronal stem cells and their response to stress.

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Figures

Figure 1
Figure 1
Redox potential determines whether Sirt1 drives cells towards neuronal or astroglial fates. (a) In an oxidizing environment, Sirt1 forms a complex with Hes1 on the Mash1 promoter, deacetylates histones and recruits repressor proteins such as TLE1. This inhibits transcription of Mash1 and drives the cell towards an astrocyte fate. (b) In a reducing environment, Sirt1 does not bind to Hes1 on the Mash1 promoter. Instead, Hes1 recruits CBP, which activates Mash1 transcription and stimulates the stem cell to assume a neuronal fate.
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