The human NAD metabolome: Functions, metabolism and compartmentalization

Aa, Nikiforov; Kulikova, Veronika; Ziegler, Mathias

doi:10.3109/10409238.2015.1028612

Cited by 203 publications

(198 citation statements)

References 173 publications

(209 reference statements)

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“…2A). In addition, NAD + is consumed by a number of important enzymes: e.g., the sirtuins that link metabolism to a variety of cellular processes including aging, the poly-and mono-ADP ribosylases that participate in cell death pathways, and other enzymes that promote metabolic homeostasis via monitoring NAD + levels (37).…”

Section: Brain Metabolism In Children and Adultsmentioning

confidence: 99%

Feeding the brain and nurturing the mind: Linking nutrition and the gut microbiota to brain development

Goyal

Venkatesh

Milbrandt

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

123

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The human gut contains a microbial community composed of tens of trillions of organisms that normally assemble during the first 2-3 y of postnatal life. We propose that brain development needs to be viewed in the context of the developmental biology of this "microbial organ" and its capacity to metabolize the various diets we consume. We hypothesize that the persistent cognitive abnormalities seen in children with undernutrition are related in part to their persistent gut microbiota immaturity and that specific regions of the brain that normally exhibit persistent juvenile (neotenous) patterns of gene expression, including those critically involved in various higher cognitive functions such as the brain's default mode network, may be particularly vulnerable to the effects of microbiota immaturity in undernourished children. Furthermore, we postulate that understanding the interrelationships between microbiota and brain metabolism in childhood undernutrition could provide insights about responses to injury seen in adults. We discuss approaches that can be used to test these hypotheses, their ramifications for optimizing nutritional recommendations that promote healthy brain development and function, and the potential societal implications of this area of investigation.In 2001, Raichle et al. published a paper in PNAS describing the default mode network (DMN) (1). This network consists of discrete, bilateral, and symmetrical areas in parietal, prefrontal, and temporal cortices of the human, nonhuman primate, feline, and rodent brain (2). The DMN consistently decreases its activity during the performance of novel, attention-demanding, non-self-referential tasks compared with quiet repose and more automatic activities. Another unique feature of the DMN is that it exhibits an overall high metabolic rate. The discovery of the DMN with its unique constellation of features has reignited a longstanding interest in the significance of the brain's ongoing or intrinsic activity (currently dubbed the brain's "resting state") (3), which accounts for the vast majority of its enormous energy cost. We believe it is timely to provide a Perspective that challenges us to consider how this cost is being met and how new knowledge gleaned from studying the development of our gut microbial communities can be leveraged to build healthy brains and minds through better nutrition.

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Section: Brain Metabolism In Children and Adultsmentioning

confidence: 99%

Feeding the brain and nurturing the mind: Linking nutrition and the gut microbiota to brain development

Goyal

Venkatesh

Milbrandt

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

123

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“…Фермент NAMPT служит лимитирующим звеном ре-циклирования и биосинтеза NAD+ в клетке. Цикли-ческие изменения уровня NAD+ в клетке являются отражением циркадного характера экспрессии гена и белка NAMPT (Revollo et al, 2004;Nakahata et al, 2009;Ramsey et al, 2009;Nikiforov et al, 2015). 3.…”

Section: предпосылкиunclassified

“…NAD+ является косубстратом деацетилазы гистонов SIRT1. Активность SIRT1 определяется уровнем NAD+, и поскольку уровень NAD+ меняется в циркадной манере, такой же характер носит и изменение актив-ности SIRT1 (Revollo et al, 2004;Nakahata et al, 2009;Nikiforov et al, 2015) (рис. 1).…”

Section: предпосылкиunclassified

“…Лимитирующим звеном биосинтеза и рециклирования NAD+ является фермент NAMPT. Экспрессия гена Nampt регулируется транскрипционным фактором CLOCK/ BMAL1 и проявляет циркадные осцилляции на уровне мРНК и белка (Revollo et al, 2004;Nakahata et al, 2009;Ramsey et al, 2009;Yoshino et al, 2011;Stein, Imai, 2014;Nikiforov et al, 2015). В соответствии с этим уровень NAD+, а значит и активность SIRT1, также изменяется с 24-часовым периодом.…”

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Computational model for mammalian circadian oscillator: interacting with NAD+/SIRT1 pathway and age-related changes in gene expression of circadian oscillator

Podkolodnyy¹,

Tverdokhleb²,

Podkolodnaya³

2016

Vestn. VOGiS

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Studies of the last decade reveal a new sight on the possible link between aging processes and circadian rhythm. New data on the role of the NAD+-dependent histone deacetylase SIRT1 in the integration of regulation pathways for circadian rhythms and metabolism as well as data on a new function of the NAD+ as the "metabolic oscillator" open a promising direction in this area. In the paper we suggested a modification and extension of the most detailed model for the circadian oscillator developed by Kim and Forger (2012). We included the additional feedback of the oscillator which concerns genes/proteins NAMPT, SIRT1, and also NAM, NAD+. The regulation of transcription for gene NAMPT by transcription factor CLOCK/BMAL1 determine the appropriate rhythm of mRNA and protein NAMPT expression. Since an enzyme product of this gene is a key in the pathway of biosynthesis and recycling of NAD+, therefore the circadian rhythm is also characteristic for the fluctuations in the level of this coenzyme and in the activity of NAD+-dependent histone deacetylase SIRT1. The deacetylation of circadian oscillator components by this enzyme closes the feedback mediated through this pathway. In particular, the effects of SIRT1 in circadian oscillator are the gain of degradation of protein Per2, increasing of the gene Bmal1 transcription, deacetylation of chromatin in regulatory regions of circadian oscillator genes in the E-boxes area with subsequent suppression of transcription. We took into account all of these processes in our extended model of the circadian oscillator. Based on the experimental Исследования последнего десятилетия позволяют по-новому посмотреть на возможную связь между процессами старения и циркадным ритмом. Одно из перспективных направлений в этой области появилось в связи с новыми данными относительно участия NAD+-зависимой деацетилазы гистонов SIRT1 в интегра-ции путей регуляции циркадного ритма и метаболизма и новой функции NAD+ как «метаболического осциллятора». Представлена модифицированная и расширенная нами наиболее детальная модель циркадного осциллятора, разработанная в 2012 г. J.K. Kim и D.B. Forger. В нее включена дополнительная обратная связь осциллятора с участием генов/белков NAMPT, SIRT1, а также NAM, NAD+. Участие транскрипционного фактора CLOCK/BMAL1 в регу-ляции транскрипции гена NAMPT определяет соответствующую ритмичность экспрессии мРНК и белка NAMPT. Поскольку фер-мент, продукт этого гена, является ключевым в пути биосинтеза и рециклирования NAD+, циркадный ритм характерен и для колебания уровня этого кофермента и активности NAD+-зави си-мой деацетилазы гистонов SIRT1. Деацетилирование этим фер-ментом компонент циркадного осциллятора замыкает обратную связь, опосредуемую этим путем. В частности, среди эффектов SIRT1 в циркадном осцилляторе можно выделить усиление дегра-дации белка Per2, усиление транскрипции гена Bmal1, деацети ли -рование хроматина регуляторных областей генов циркадного осциллятора в области E-боксов с последующим подавлением транскрипции. Все эти процессы представлены в предл...

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“…In this regard, the study of nicotinamide adenine dinucleotide (NAD+) is prominent and appropriate given the essential functions it performs, such as energy metabolism, defense against oxidative stress, and cellular regulation [3].…”

Section: Introductionmentioning

confidence: 99%

Study of Specific Region of Plasmodium falciparum Nicotinamide/Nicotinate Mononucleotide Adenylyl Transferase (PfNMNAT): Characterizing a Possible Therapeutic Target

Ca¹,

Cy²,

Contreras-Rodríguez³

et al. 2017

J Mol Genet Med

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The human NAD metabolome: Functions, metabolism and compartmentalization

Cited by 203 publications

References 173 publications

Feeding the brain and nurturing the mind: Linking nutrition and the gut microbiota to brain development

Feeding the brain and nurturing the mind: Linking nutrition and the gut microbiota to brain development

Computational model for mammalian circadian oscillator: interacting with NAD+/SIRT1 pathway and age-related changes in gene expression of circadian oscillator

Study of Specific Region of Plasmodium falciparum Nicotinamide/Nicotinate Mononucleotide Adenylyl Transferase (PfNMNAT): Characterizing a Possible Therapeutic Target

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