SIRT1是在DNA修復和基因組穩(wěn)定性中所涉及的一種脫乙酰酶,，最初是在非哺乳動物模型系統(tǒng)中作為壽命的一個調(diào)控因子被識別出的,。雖然人們認為它在正常腦生理中發(fā)揮功能，但過去并不知道SIRT1是否參與高等腦功能?，F(xiàn)在,，Gao等人演示了SIRT1的這樣一個作用：其激發(fā)能增強突觸強度和記憶形成。這些依賴于SIRT1的效應是通過一個“轉(zhuǎn)錄后”機制調(diào)控的,，該機制涉及CREB激發(fā)和miR-134生成,。SIRT1激發(fā)、 miR-134水平和突觸蛋白之間的這種互動構成彈性調(diào)控的一個以前未被識別出的機制,，并且表明,，SIRT1激發(fā)對于涉及認知損傷的神經(jīng)退行性疾病可能具有治療潛力。（生物谷Bioon.com）
生物谷推薦原文出處：
Nature doi:10.1038/nature09271
A novel pathway regulates memory and plasticity via SIRT1 and miR-134
Jun Gao,Wen-Yuan Wang,Ying-Wei Mao,Johannes Gr?ff,Ji-Song Guan,Ling Pan,Gloria Mak,Dohoon Kim,Susan C. Su& Li-Huei Tsai
The NAD-dependent deacetylase Sir2 was initially identified as a mediator of replicative lifespan in budding yeast and was subsequently shown to modulate longevity in worms and flies1, 2. Its mammalian homologue, SIRT1, seems to have evolved complex systemic roles in cardiac function, DNA repair and genomic stability. Recent studies suggest a functional relevance of SIRT1 in normal brain physiology and neurological disorders. However, it is unknown if SIRT1 has a role in higher-order brain functions. We report that SIRT1 modulates synaptic plasticity and memory formation via a microRNA-mediated mechanism. Activation of SIRT1 enhances, whereas its loss-of-function impairs, synaptic plasticity. Surprisingly, these effects were mediated via post-transcriptional regulation of cAMP response binding protein (CREB) expression by a brain-specific microRNA, miR-134. SIRT1 normally functions to limit expression of miR-134 via a repressor complex containing the transcription factor YY1, and unchecked miR-134 expression following SIRT1 deficiency results in the downregulated expression of CREB and brain-derived neurotrophic factor (BDNF), thereby impairing synaptic plasticity. These findings demonstrate a new role for SIRT1 in cognition and a previously unknown microRNA-based mechanism by which SIRT1 regulates these processes. Furthermore, these results describe a separate branch of SIRT1 signalling, in which SIRT1 has a direct role in regulating normal brain function in a manner that is disparate from its cell survival functions, demonstrating its value as a potential therapeutic target for the treatment of central nervous system disorders.
