Targeting sirtuin 1 to improve metabolism: all you need is NAD(+)?

Targeting sirtuin 1 to improve metabolism: all you need is NAD(+)?
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靶向Sirtuin 1以改善新陈代谢:您所需要的是NAD(+)?

DOI:
10.1124/pr.110.003905
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发表时间:
2012-01
影响因子:
21.1
通讯作者:
Auwerx J
Auwerx J
中科院分区:
医学1区
文献类型:
--
作者:
Cantó C;Auwerx J

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SIRT1是一种进化上保守的NAD+依赖性脱乙酰酶,处于代谢控制的顶峰,从酵母到人类。SIRT1感知细胞内NAD+水平的变化,这反映了能量水平,并使用此信息来调整细胞能量输出,使其与细胞能量需求相匹配。一般而言,但不限于此,SIRT1激活诱导的变化本质上是转录的,与线粒体代谢和抗氧化保护的增加有关。这些有吸引力的特征已经验证了SIRT1作为代谢疾病管理中的治疗靶点,并促使深入研究以确定药理学SIRT1激活剂。在这篇综述中,我们将首先概述SIRT1生物学,特别关注其在代谢控制中的作用。然后,我们将分析目前用于激活SIRT1的策略的利弊,并探索新出现的证据表明,NAD+水平的调节可以提供实现这些目标的有效方法。
SIRT1 is an evolutionary conserved NAD+-dependent deacetylase that is at the pinnacle of metabolic control, all the way from yeast to humans. SIRT1 senses changes in intracellular NAD+ levels, which reflect energy level, and uses this information to adapt the cellular energy output, such that the it matches cellular energy requirements. Generally, but not exclusively, the changes induced by SIRT1 activation are transcriptional in nature and are related to an increase in mitochondrial metabolism and antioxidant protection. These attractive features have validated SIRT1 as a therapeutic target in the management of metabolic disease and prompted an intensive search to identify pharmacological SIRT1 activators. In this review we will first give an overview of the SIRT1 biology with a particular focus on its role in metabolic control. We will then analyze the pros and cons of the current strategies used to activate SIRT1 and explore the emerging evidence indicating that modulation of NAD+ levels could provide an effective way to achieve such goals.
DOI: 10.1016/j.cmet.2011.03.013
发表时间: 2011-04-06
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