NAD+ and vitamin B3:: From metabolism to therapies
NAD+ and vitamin B3:: From metabolism to therapies
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DOI：
10.1124/jpet.107.120758
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发表时间：
2008-03-01
影响因子：
3.5
通讯作者：
Sauve, Anthony A.
中科院分区：
文献类型：
--
作者：
Sauve, Anthony A.
随着烟酸（烟酸）的使用已成为治疗高脂血症的主要疗法，并且人们认识到烟酰胺可以在多种疾病状态（包括缺血/再灌注）下保护组织和 NAD（+） 代谢，NAD（+）代谢在健康和疾病中的作用越来越受到人们的关注。此外，越来越多的证据支持 NAD(+) 代谢调节重要的生物效应（包括寿命）的观点。 NAD(+) 通过聚 (ADP-核糖) 聚合酶、单 ADP-核糖基转移酶和最近鉴定的沉默调节蛋白 (sirtuin) 酶发挥有效作用。这些酶催化蛋白质修饰，例如 ADP 核糖基化和脱乙酰化，导致蛋白质功能发生变化。这些酶调节细胞凋亡、DNA 修复、应激抵抗、代谢和内分泌信号传导，表明这些酶和/或 NAD(+) 代谢可以作为治疗益处的目标。本综述考虑了人类和微生物中 NAD(+) 代谢的最新知识，包括对调节 NAD(+) 生物合成途径的机制的新见解、烟酰胺和烟酸作为药物制剂的当前使用，以及针对调节 NAD(+) 生物合成以治疗人类疾病和感染的药物设计机会。
The role of NAD(+) metabolism in health and disease is of increased interest as the use of niacin (nicotinic acid) has emerged as a major therapy for treatment of hyperlipidemias and with the recognition that nicotinamide can protect tissues and NAD(+) metabolism in a variety of disease states, including ischemia/reperfusion. In addition, a growing body of evidence supports the view that NAD(+) metabolism regulates important biological effects, including lifespan. NAD(+) exerts potent effects through the poly(ADP-ribose) polymerases, mono-ADP-ribosyltransferases, and the recently characterized sirtuin enzymes. These enzymes catalyze protein modifications, such as ADP-ribosylation and deacetylation, leading to changes in protein function. These enzymes regulate apoptosis, DNA repair, stress resistance, metabolism, and endocrine signaling, suggesting that these enzymes and/or NAD(+) metabolism could be targeted for therapeutic benefit. This review considers current knowledge of NAD(+) metabolism in humans and microbes, including new insights into mechanisms that regulate NAD(+) biosynthetic pathways, current use of nicotinamide and nicotinic acid as pharmacological agents, and opportunities for drug design that are directed at modulation of NAD(+) biosynthesis for treatment of human disorders and infections.