A novel pathway regulates memory and plasticity via SIRT1 and miR-134

Jun Gao, Wen-Yuan Wang, Ying-Wei Mao, Johannes Gräff, Ji-Song Guan, Ling Pan, Gloria Mak, Dohoon Kim, Susan C. Su and Li-Huei Tsai ()
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Jun Gao: Picower Institute for Learning and Memory, Massachusetts Institute of Technology
Wen-Yuan Wang: Picower Institute for Learning and Memory, Massachusetts Institute of Technology
Ying-Wei Mao: Picower Institute for Learning and Memory, Massachusetts Institute of Technology
Johannes Gräff: Picower Institute for Learning and Memory, Massachusetts Institute of Technology
Ji-Song Guan: Picower Institute for Learning and Memory, Massachusetts Institute of Technology
Ling Pan: Picower Institute for Learning and Memory, Massachusetts Institute of Technology
Gloria Mak: Picower Institute for Learning and Memory, Massachusetts Institute of Technology
Dohoon Kim: Picower Institute for Learning and Memory, Massachusetts Institute of Technology
Susan C. Su: Picower Institute for Learning and Memory, Massachusetts Institute of Technology
Li-Huei Tsai: Picower Institute for Learning and Memory, Massachusetts Institute of Technology

Nature, 2010, vol. 466, issue 7310, 1105-1109

Abstract: A role for SIRT1 in memory SIRT1 is a deacetylase involved in DNA repair and genomic stability that was originally identified in non-mammalian model systems as a modulator of longevity. Although it was thought to function in normal brain physiology, it was not known whether SIRT1 participates in higher-order brain functions. Gao et al. now demonstrate such a role for SIRT1: its activation enhances synaptic strength and memory formation. These SIRT1-dependent effects are regulated through a post-transcriptional mechanism involving CREB activation and miR-134 production. This interplay between SIRT1 activation, miR-134 levels and synaptic proteins constitutes a previously unrecognized mechanism of plasticity regulation, and suggests that SIRT1 activation may have therapeutic potential in neurodegenerative diseases involving cognitive impairment.

Date: 2010
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DOI: 10.1038/nature09271

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