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Sirt1 Promotes Axonogenesis by Deacetylation of Akt and Inactivation of GSK3

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Abstract

Accumulating evidence shows that Sirt1 regulates a variety of neurological functions through the deacetylation of many proteins besides histone; however, the literature on the relationship between Sirt1 and axonal outgrowth is limited. Here, we first demonstrated that Sirt1 was located in the axon, especially in the growth cone. Then, we found that genetic inhibition of Sirt1 retarded axonal development in embryonic hippocampal neurons, whereas genetic and pharmacologic upregulation of Sirt1 promoted not only the formation but also the elongation of axons. Sirt1 can deacetylate and thus activate Akt, and inhibition of Akt significantly reversed the axonogenesis induced by Sirt1 overexpression. We also found that Sirt1 inhibited the activity of glycogen synthase kinase 3 (GSK3), whereas activation of GSK3 could abolish the effect of Sirt1. These results suggest that Sirt1 promotes axonogenesis by deacetylating Akt and thereby activates the Akt/GSK3 pathway, which could be a promising therapeutic target for axonopathy.

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Acknowledgments

This work was supported by the National Nature Scientific Fund of China (81271392) and the Fund of Affiliated Hospital of Logistics College of Chinese People’s Armed Police Forces (FYM201219).

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Authors and Affiliations

  1. Institute of Traumatic Brain Injury and Neurology, Department of Neurology, Pingjin Hospital, Logistics College of Chinese People’s Armed Police Forces, Tianjin, 300162, China

    Xiao-hong Li, Chong Chen, Yue Tu, Hong-tao Sun, Ming-liang Zhao, Shi-xiang Cheng, Yang Qu & Sai Zhang

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  1. Xiao-hong Li
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Correspondence to Sai Zhang.

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Xiao-hong Li and Chong Chen contributed equally to this study.

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Li, Xh., Chen, C., Tu, Y. et al. Sirt1 Promotes Axonogenesis by Deacetylation of Akt and Inactivation of GSK3. Mol Neurobiol 48, 490–499 (2013). https://doi.org/10.1007/s12035-013-8437-3

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