NAD(+) metabolism: Bioenergetics, signaling and manipulation for therapy.
NAD(+) metabolism: Bioenergetics, signaling and manipulation for therapy.
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DOI：
10.1016/j.bbapap.2016.06.014
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发表时间：
2016-12
期刊：
影响因子：
--
通讯作者：
Sauve AA
中科院分区：
文献类型：
--
作者：
Yang Y;Sauve AA
我们调查的科学知识的历史发展，围绕维生素B3，并描述了维生素B3的活性代谢物形式，吡啶二核苷酸NAD+和NADP+，这是必不可少的能量代谢，细胞保护和生物合成的细胞过程。NAD+代谢的动态触发了与效应物（sirtuins，PARP和CD 38）偶联的主要信号传导过程，这些效应物使用NAD+作为效应底物重新编程细胞代谢，这一新的认识使NAD+的研究重新焕发了活力。细胞适应包括刺激线粒体生物发生，这是调节细胞和组织生理以减少营养可用性和/或增加能量需求的基本过程。几种代谢途径会聚到NAD+，包括Dahan衍生的从头途径、烟酰胺补救途径、烟酸补救途径和掺入烟酰胺核苷和烟酸核苷的核苷补救途径。关键发现突出了靶向NAD+生物合成途径治疗人类疾病的治疗潜力。最近出现的理解是，NAD+稳态易受衰老和疾病过程的影响，这刺激了测试，以确定细胞或组织NAD+的补充或增加是否可以对衰老或疾病表型产生改善作用。这种实验方法已经提供了几个概念成功的证明，证明补充或增加NAD+浓度可以提供改善或治疗益处。因此，NAD+代谢途径可以提供用于评估和调节生物体健康的关键生物标志物和参数。
We survey the historical development of scientific knowledge surrounding Vitamin B3, and describe the active metabolite forms of Vitamin B3, the pyridine dinucleotides NAD+ and NADP+ which are essential to cellular processes of energy metabolism, cell protection and biosynthesis. The study of NAD+ has become reinvigorated by new understandings that dynamics within NAD+ metabolism trigger major signaling processes coupled to effectors (sirtuins, PARPs, and CD38) that reprogram cellular metabolism using NAD+ as an effector substrate. Cellular adaptations include stimulation of mitochondrial biogenesis, a process fundamental to adjusting cellular and tissue physiology to reduced nutrient availability and/or increased energy demand. Several metabolic pathways converge to NAD+, including tryptophan-derived de novo pathways, nicotinamide salvage pathways, nicotinic acid salvage and nucleoside salvage pathways incorporating nicotinamide riboside and nicotinic acid riboside. Key discoveries highlight a therapeutic potential for targeting NAD+ biosynthetic pathways for treatment of human diseases. A recent emergence of understanding that NAD+ homeostasis is vulnerable to aging and disease processes has stimulated testing to determine if replenishment or augmentation of cellular or tissue NAD+ can have ameliorative effects on aging or disease phenotypes. This experimental approach has provided several proof of concept successes demonstrating that replenishment or augmentation of NAD+ concentrations can provide ameliorative or curative benefits. Thus NAD+ metabolic pathways can provide key biomarkers and parameters for assessing and modulating organism health.
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影响因子：
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作者：
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DOI：
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影响因子：
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DOI：
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发表时间：
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影响因子：
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作者：
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