Role of NAD(+) in regulating cellular and metabolic signaling pathways.
Role of NAD(+) in regulating cellular and metabolic signaling pathways.
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DOI：
10.1016/j.molmet.2021.101195
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发表时间：
2021-07
影响因子：
8.1
通讯作者：
Bagga P
中科院分区：
文献类型：
--
作者：
Amjad S;Nisar S;Bhat AA;Shah AR;Frenneaux MP;Fakhro K;Haris M;Reddy R;Patay Z;Baur J;Bagga P
烟酰胺腺嘌呤二核苷酸（NAD+）是存在于每个活细胞中的关键辅酶，参与与细胞生物能量学相关的无数代谢过程。出于这个原因，NAD+经常在衰老，癌症，神经退行性疾病和代谢疾病的背景下进行研究。细胞NAD+耗竭与受损的适应性细胞应激反应、受损的神经元可塑性、受损的DNA修复和细胞衰老相关。越来越多的证据表明，在各种疾病中使用NAD+前体提高NAD+水平的功效。本文综述了NAD+在衰老和其他病理学中的作用，并讨论了潜在的治疗靶点。NAD+/NADH比率或NAD+库大小的改变可导致生物系统的脱轨，并导致各种神经退行性疾病、衰老和肿瘤发生。由于NAD+/NADH在细胞内不同位置的不同分布，受损的NAD+依赖性过程在人类中的直接作用仍然不确定。在这方面，需要进行纵向研究来量化NAD+及其相关代谢物。未来的研究应侧重于通过与NAD+合成和降解相关的途径测量通量。NAD+调节能量代谢、DNA损伤修复、基因表达和应激反应。NAD+的退化有助于多种代谢紊乱、癌症和神经退行性疾病的进展。在临床前模型中，烟酰胺单甘肽和烟酰胺核苷提高不同组织中的NAD+水平。对遗传模型的成像研究可以说明NAD+代谢的途径及其下游功能效应。确定通过使用NAD前体恢复NAD+的益处的人类临床试验正在进行中。
Nicotinamide adenine dinucleotide (NAD+), a critical coenzyme present in every living cell, is involved in a myriad of metabolic processes associated with cellular bioenergetics. For this reason, NAD+ is often studied in the context of aging, cancer, and neurodegenerative and metabolic disorders. Cellular NAD+ depletion is associated with compromised adaptive cellular stress responses, impaired neuronal plasticity, impaired DNA repair, and cellular senescence. Increasing evidence has shown the efficacy of boosting NAD+ levels using NAD+ precursors in various diseases. This review provides a comprehensive understanding into the role of NAD+ in aging and other pathologies and discusses potential therapeutic targets. An alteration in the NAD+/NADH ratio or the NAD+ pool size can lead to derailment of the biological system and contribute to various neurodegenerative disorders, aging, and tumorigenesis. Due to the varied distribution of NAD+/NADH in different locations within cells, the direct role of impaired NAD+-dependent processes in humans remains unestablished. In this regard, longitudinal studies are needed to quantify NAD+ and its related metabolites. Future research should focus on measuring the fluxes through pathways associated with NAD+ synthesis and degradation. NAD+ regulates energy metabolism, DNA damage repair, gene expression, and stress response. NAD+ deterioration contributes to the progression of multiple metabolic disorders, cancers, and neurodegenerative diseases. Nicotinamide mononucleotide and nicotinamide riboside raise NAD+ levels in different tissues in preclinical models. Imaging studies on genetic models can illustrate the pathways of NAD+metabolism and their downstream functional effects. Human clinical trials to determine benefits of restoration of NAD+ by using NAD precursors are in progress.
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影响因子：
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作者：
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通讯作者：
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