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NAD+ increase AND supplements

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https://www.readbyqxmd.com/read/29570846/neuroprotective-effects-of-creatine-in-the-cmvmjd135-mouse-model-of-spinocerebellar-ataxia-type-3
#1
Sara Duarte-Silva, Andreia Neves-Carvalho, Carina Soares-Cunha, Joana M Silva, Andreia Teixeira-Castro, Rita Vieira, Anabela Silva-Fernandes, Patrícia Maciel
BACKGROUND AND OBJECTIVE: Mitochondrial dysfunction has been implicated in several neurodegenerative diseases. Creatine administration increases concentration of the energy buffer phosphocreatine, exerting protective effects in the brain. We evaluate whether a creatine-enriched diet would be beneficial for a mouse model of spinocerebellar ataxia type 3, a genetically defined neurodegenerative disease for which no treatment is available. METHODS: We performed 2 independent preclinical trials using the CMVMJD135 mouse model (treating 2 groups of animals with different disease severity) and wild-type mice, to which 2% creatine was provided for 19 (preclinical trial 1) or 29 (preclinical trial 2) weeks, starting at a presymptomatic age...
March 23, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29560544/anti-cancer-labdane-diterpenoids-from-adventitious-roots-of-andrographis-paniculata-augmentation-of-production-prospect-endowed-with-pathway-gene-expression
#2
Sailendra Singh, Pallavi Pandey, Sumit Ghosh, Suchitra Banerjee
Andrographolide (AD) is the time-honoured pharmacologically active constituent of the traditionally renowned medicinal plant-Andrographis paniculata. Advancements in the target-oriented drug discovery process have further unravelled the immense therapeutic credibility of another unique molecule-neoandrographolide (NAD). The escalated market demand of these anti-cancer diterpenes is increasingly facing unrelenting hurdles of demand and supply disparity, attributable to their limited yield. Callus and adventitious root cultures were generated to explore their biosynthetic potentials which first time revealed NAD production along with AD...
March 20, 2018: Protoplasma
https://www.readbyqxmd.com/read/29514072/nicotinamide-improves-aspects-of-healthspan-but-not-lifespan-in-mice
#3
Sarah J Mitchell, Michel Bernier, Miguel A Aon, Sonia Cortassa, Eun Young Kim, Evandro F Fang, Hector H Palacios, Ahmed Ali, Ignacio Navas-Enamorado, Andrea Di Francesco, Tamzin A Kaiser, Tyler B Waltz, Ning Zhang, James L Ellis, Peter J Elliott, David W Frederick, Vilhelm A Bohr, Mark S Schmidt, Charles Brenner, David A Sinclair, Anthony A Sauve, Joseph A Baur, Rafael de Cabo
The role in longevity and healthspan of nicotinamide (NAM), the physiological precursor of NAD+ , is elusive. Here, we report that chronic NAM supplementation improves healthspan measures in mice without extending lifespan. Untargeted metabolite profiling of the liver and metabolic flux analysis of liver-derived cells revealed NAM-mediated improvement in glucose homeostasis in mice on a high-fat diet (HFD) that was associated with reduced hepatic steatosis and inflammation concomitant with increased glycogen deposition and flux through the pentose phosphate and glycolytic pathways...
March 6, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29509007/lycopene-supplementation-attenuates-oxidative-stress-neuroinflammation-and-cognitive-impairment-in-aged-cd-1-mice
#4
Beita Zhao, Hua Liu, Jiamin Wang, Pujie Liu, Xintong Tan, Bo Ren, Zhigang Liu, Xuebo Liu
Carotenoid pigment lycopene (LYC) possesses several types of properties such as antioxidative, anti-inflammatory, and neuroprotective. This study examined the effects of dietary supplementation with LYC on age-induced cognitive impairment, and the potential underlying mechanisms. Behavioral tests revealed that chronic LYC supplementation alleviated age-associated memory loss and cognitive defects. Histological and immunofluorescence staining results indicated that LYC treatment reversed age-associated neuronal damage and synaptic dysfunction in the brain...
March 6, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29432159/nad-supplementation-normalizes-key-alzheimer-s-features-and-dna-damage-responses-in-a-new-ad-mouse-model-with-introduced-dna-repair-deficiency
#5
Yujun Hou, Sofie Lautrup, Stephanie Cordonnier, Yue Wang, Deborah L Croteau, Eduardo Zavala, Yongqing Zhang, Kanako Moritoh, Jennifer F O'Connell, Beverly A Baptiste, Tinna V Stevnsner, Mark P Mattson, Vilhelm A Bohr
Emerging findings suggest that compromised cellular bioenergetics and DNA repair contribute to the pathogenesis of Alzheimer's disease (AD), but their role in disease-defining pathology is unclear. We developed a DNA repair-deficient 3xTgAD/Polβ+/- mouse that exacerbates major features of human AD including phosphorylated Tau (pTau) pathologies, synaptic dysfunction, neuronal death, and cognitive impairment. Here we report that 3xTgAD/Polβ+/- mice have a reduced cerebral NAD+ /NADH ratio indicating impaired cerebral energy metabolism, which is normalized by nicotinamide riboside (NR) treatment...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29420256/nicotinamide-phosphoribosyltransferase-deficiency-potentiates-the-anti-proliferative-activity-of-methotrexate-through-enhanced-depletion-of-intracellular-atp
#6
Rakesh K Singh, Leon van Haandel, Daniel P Heruth, Shui Q Ye, J Steven Leeder, Mara L Becker, Ryan S Funk
Lower plasma nicotinamide phosphoribosyltransferase (NAMPT) levels are associated with improved response to methotrexate (MTX) in patients with juvenile idiopathic arthritis (JIA). Cell-based studies confirmed that reduced cellular NAMPT activity potentiates the pharmacologic activity of MTX, however the mechanism of this interaction has yet to be defined. Therefore, in this study we investigate the mechanism of enhanced pharmacologic activity of MTX in NAMPT-deficient A549 cells. The siRNA-based silencing of NAMPT expression resulted in a greater than three-fold increase in the sensitivity to MTX (p<0...
February 2, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29410706/enhanced-isopropanol-butanol-ethanol-mixture-production-through-manipulation-of-intracellular-nad-p-h-level-in-the-recombinant-clostridium-acetobutylicum-xy16
#7
Chao Wang, Fengxue Xin, Xiangping Kong, Jie Zhao, Weiliang Dong, Wenming Zhang, Jiangfeng Ma, Hao Wu, Min Jiang
Background: The formation of by-products, mainly acetone in acetone-butanol-ethanol (ABE) fermentation, significantly affects the solvent yield and downstream separation process. In this study, we genetically engineered Clostridium acetobutylicum XY16 isolated by our lab to eliminate acetone production and altered ABE to isopropanol-butanol-ethanol (IBE). Meanwhile, process optimization under pH control strategies and supplementation of calcium carbonate were adopted to investigate the interaction between the reducing force of the metabolic networks and IBE production...
2018: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/29408602/hepatic-nad-levels-and-nampt-abundance-are-unaffected-during-prolonged-high-fat-diet-consumption-in-c57bl-6jbomtac-mice
#8
Morten Dall, Melanie Penke, Karolina Sulek, Madlen Matz-Soja, Birgitte Holst, Antje Garten, Wieland Kiess, Jonas T Treebak
Dietary supplementation of nicotinamide adenine dinucleotide (NAD+) precursors has been suggested as a treatment for non-alcoholic fatty liver disease and obesity. In the liver, NAD+ is primarily generated by nicotinamide phosphoribosyltransferase (NAMPT), and hepatic levels of NAMPT and NAD+ have been reported to be dependent on age and body composition. The aim of the present study was to identify time-course-dependent changes in hepatic NAD content and NAD+ salvage capacity in mice challenged with a high-fat diet (HFD)...
February 1, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29393101/resveratrol-promotes-recovery-of-hearing-following-intense-noise-exposure-by-enhancing-cochlear-sirt1-activity
#9
Hao Xiong, Yongkang Ou, Yaodong Xu, Qiuhong Huang, Jiaqi Pang, Lan Lai, Yiqing Zheng
The sirtuin SIRT1 is a highly conserved nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylase known to have protective effects against a wide range of neurological disorders. In the present study, we discovered that C57BL/6 mice fed a long-term diet supplemented with high-dose resveratrol exhibited increased cochlear SIRT1 activity and presented a better recovery of hearing and less loss of hair cells after intense noise exposure compared with those fed a standard chew. Moreover, resveratrol attenuated cochlear SIRT1 decrease and reduced oxidative stress in the cochlea after noise exposure...
2017: Audiology & Neuro-otology
https://www.readbyqxmd.com/read/29232252/nicotinamide-adenine-dinucleotide-and-its-related-precursors-for-the-treatment-of-alzheimer-s-disease
#10
Nady Braidy, Ross Grant, Perminder S Sachdev
PURPOSE OF REVIEW: The current review discusses the biology and metabolism of the essential pyridine nucleotide nicotinamide adenine dinucleotide (NAD+) in the central nervous system. We also review recent work suggesting important neuroprotective effects that may be associated with the promotion of NAD+ levels through NAD+ precursors against Alzheimer's disease. RECENT FINDINGS: Perturbations in the physiological homoeostatic state of the brain during the ageing process can lead to impaired cellular function, and ultimately leads to loss of brain integrity and accelerates cognitive and memory decline...
March 2018: Current Opinion in Psychiatry
https://www.readbyqxmd.com/read/29217642/nicotinamide-riboside-preserves-cardiac-function-in-a-mouse-model-of-dilated-cardiomyopathy
#11
Nicolas Diguet, Samuel A J Trammell, Cynthia Tannous, Robin Deloux, Jérôme Piquereau, Nathalie Mougenot, Anne Gouge, Mélanie Gressette, Boris Manoury, Jocelyne Blanc, Marie Breton, Jean-François Decaux, Gareth Lavery, István Baczkó, Joffrey Zoll, Anne Garnier, Zhenlin Li, Charles Brenner, Mathias Mericskay
Background -Myocardial metabolic impairment is a major feature in chronic heart failure (HF). As the major coenzyme in fuel oxidation and oxidative phosphorylation and a substrate for enzymes signaling energy stress and oxidative stress response, NAD+ is emerging as a metabolic target in a number of diseases including HF. Little is known on mechanisms regulating homeostasis of NAD+ in the failing heart. Methods -To explore possible alterations of NAD+ homeostasis in the failing heart, we quantified expression of NAD+ biosynthetic enzymes in human failing heart and in the heart of a mouse model of dilated cardiomyopathy (DCM) triggered by SRF transcription factor depletion in the heart (SRFHKO ) or of cardiac hypertrophy triggered by transverse aorta constriction (TAC)...
December 7, 2017: Circulation
https://www.readbyqxmd.com/read/29211728/an-open-label-non-randomized-study-of-the-pharmacokinetics-of-the-nutritional-supplement-nicotinamide-riboside-nr-and-its-effects-on-blood-nad-levels-in-healthy-volunteers
#12
Sophia E Airhart, Laura M Shireman, Linda J Risler, Gail D Anderson, G A Nagana Gowda, Daniel Raftery, Rong Tian, Danny D Shen, Kevin D O'Brien
OBJECTIVES: The co-primary objectives of this study were to determine the human pharmacokinetics (PK) of oral NR and the effect of NR on whole blood nicotinamide adenine dinucleotide (NAD+) levels. BACKGROUND: Though mitochondrial dysfunction plays a critical role in the development and progression of heart failure, no mitochondria-targeted therapies have been translated into clinical practice. Recent murine studies have reported associations between imbalances in the NADH/NAD+ ratio with mitochondrial dysfunction in multiple tissues, including myocardium...
2017: PloS One
https://www.readbyqxmd.com/read/29184669/repeat-dose-nrpt-nicotinamide-riboside-and-pterostilbene-increases-nad-levels-in-humans-safely-and-sustainably-a-randomized-double-blind-placebo-controlled-study
#13
Ryan W Dellinger, Santiago Roel Santos, Mark Morris, Mal Evans, Dan Alminana, Leonard Guarente, Eric Marcotulli
NRPT is a combination of nicotinamide riboside (NR), a nicotinamide adenine dinucleotide (NAD+) precursor vitamin found in milk, and pterostilbene (PT), a polyphenol found in blueberries. Here, we report this first-in-humans clinical trial designed to assess the safety and efficacy of a repeat dose of NRPT (commercially known as Basis). NRPT was evaluated in a randomized, double-blind, and placebo-controlled study in a population of 120 healthy adults between the ages of 60 and 80 years. The study consisted of three treatment arms: placebo, recommended dose of NRPT (NRPT 1X), and double dose of NRPT (NRPT 2X)...
2017: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/29156373/mitochondria-targeted-ubiquinone-mitoq-enhances-acetaldehyde-clearance-by-reversing-alcohol-induced-posttranslational-modification-of-aldehyde-dehydrogenase-2-a-molecular-mechanism-of-protection-against-alcoholic-liver-disease
#14
Liuyi Hao, Qian Sun, Wei Zhong, Wenliang Zhang, Xinguo Sun, Zhanxiang Zhou
Alcohol metabolism in the liver generates highly toxic acetaldehyde. Breakdown of acetaldehyde by aldehyde dehydrogenase 2 (ALDH2) in the mitochondria consumes NAD+ and generates reactive oxygen/nitrogen species, which represents a fundamental mechanism in the pathogenesis of alcoholic liver disease (ALD). A mitochondria-targeted lipophilic ubiquinone (MitoQ) has been shown to confer greater protection against oxidative damage in the mitochondria compared to untargeted antioxidants. The present study aimed to investigate if MitoQ could preserve mitochondrial ALDH2 activity and speed up acetaldehyde clearance, thereby protects against ALD...
April 2018: Redox Biology
https://www.readbyqxmd.com/read/29133854/copper-ii-binding-of-nad-p-h-flavin-oxidoreductase-nfor-enhances-its-cr-vi-reducing-ability
#15
Huawen Han, Zhenmin Ling, Tuoyu Zhou, Rong Xu, Yongxing He, Pu Liu, Xiangkai Li
Microbes can reduce hexavalent chromium Cr (VI) to the less toxic and soluble trivalent Cr (III). Copper stimulates microbial reduction of Cr (VI) by the Bacillus, Ochrobactrum, and Gluconobacter species; however, the mechanism remains unclear. In our study, the rate of Cr (VI) reduction by Staphylococcus aureus LZ-01 was increased by 210 % when supplemented with 60 μM Cu (II). A putative NAD(P)H-flavin oxidoreductase gene (nfoR) was upregulated under Cr (VI) stress. NfoR-knockout mutant displayed impaired reduction of Cr (VI) and Cu (II)-enhanced Cr (VI) reduction by nfoR isogenic mutant was attenuated in the presence of Cu (II)...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29118320/nicotinamide-mononucleotide-nmn-supplementation-ameliorates-the-impact-of-maternal-obesity-in-mice-comparison-with-exercise
#16
Golam Mezbah Uddin, Neil A Youngson, Bronte M Doyle, David A Sinclair, Margaret J Morris
Maternal overnutrition increases the risk of long-term metabolic dysfunction in offspring. Exercise improves metabolism partly by upregulating mitochondrial biogenesis or function, via increased levels of nicotinamide adenine dinucleotide (NAD+ ). We have shown that the NAD+ precursor, nicotinamide mononucleotide (NMN) can reverse some of the negative consequences of high fat diet (HFD) consumption. To investigate whether NMN can impact developmentally-set metabolic deficits, we compared treadmill exercise and NMN injection in offspring of obese mothers...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29073231/poly-adp-ribose-polymerases-inhibitors-prevent-early-mitochondrial-fragmentation-and-hepatocyte-cell-death-induced-by-h2o2
#17
Sandra M Martín-Guerrero, José A Muñoz-Gámez, María-Carmen Carrasco, Javier Salmerón, María Martín-Estebané, Miguel A Cuadros, Julio Navascués, David Martín-Oliva
Poly(ADP-ribose)polymerases (PARPs) are a family of NAD+ consuming enzymes that play a crucial role in many cellular processes, most clearly in maintaining genome integrity. Here, we present an extensive analysis of the alteration of mitochondrial morphology and the relationship to PARPs activity after oxidative stress using an in vitro model of human hepatic cells. The following outcomes were observed: reactive oxygen species (ROS) induced by oxidative treatment quickly stimulated PARPs activation, promoted changes in mitochondrial morphology associated with early mitochondrial fragmentation and energy dysfunction and finally triggered apoptotic cell death...
2017: PloS One
https://www.readbyqxmd.com/read/29054583/dietary-resveratrol-increases-mid-life-fecundity-of-female-nothobranchius-guentheri
#18
Youngjoo Lee, Andrew C Drake, Nicholas O Thomas, Lindsey G Ferguson, Patrick E Chappell, Kate Petersen Shay
The decline of female reproductive function is an early phenotype of aging in humans, occurring only midway through the lifespan. Yet the number of women delaying pregnancy continues to rise in industrialized societies due to personal or socioeconomic circumstances, often resulting in subfertility or difficulty conceiving. There are few defined mechanisms associated with this etiology, and equally few effective therapies. To combat this problem, we used a novel emerging model, Nothobranchius guentheri, that recapitulates the age-associated spectrum of changes that adversely affect human fertility...
October 18, 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/29021282/methionine-metabolism-is-essential-for-sirt1-regulated-mouse-embryonic-stem-cell-maintenance-and-embryonic-development
#19
Shuang Tang, Yi Fang, Gang Huang, Xiaojiang Xu, Elizabeth Padilla-Banks, Wei Fan, Qing Xu, Sydney M Sanderson, Julie F Foley, Scotty Dowdy, Michael W McBurney, David C Fargo, Carmen J Williams, Jason W Locasale, Ziqiang Guan, Xiaoling Li
Methionine metabolism is critical for epigenetic maintenance, redox homeostasis, and animal development. However, the regulation of methionine metabolism remains unclear. Here, we provide evidence that SIRT1, the most conserved mammalian NAD+ -dependent protein deacetylase, is critically involved in modulating methionine metabolism, thereby impacting maintenance of mouse embryonic stem cells (mESCs) and subsequent embryogenesis. We demonstrate that SIRT1-deficient mESCs are hypersensitive to methionine restriction/depletion-induced differentiation and apoptosis, primarily due to a reduced conversion of methionine to S-adenosylmethionine...
November 2, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28970254/silybin-inhibits-nlrp3-inflammasome-assembly-through-the-nad-sirt2-pathway-in-mice-with-nonalcoholic-fatty-liver-disease
#20
Bangling Zhang, Dan Xu, Linlin She, Zixia Wang, Na Yang, Runbin Sun, Yirui Zhang, Caixia Yan, Qingli Wei, Jiye Aa, Baolin Liu, Guangji Wang, Yuan Xie
Silybin is one of the effective, traditional Chinese medicines used as a hepatoprotective agent in nonalcoholic fatty liver disease (NAFLD) therapy worldwide, and the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome has been recognized as an important factor involved in NAFLD development. However, little is known about the mechanisms of silybin in the regulation of high-fat diet (HFD)-induced liver inflammation. In our study, we found that silybin inhibited endoplasmic reticulum stress and NLRP3 inflammasome activation in the livers of HFD-fed mice and in cultured hepatocytes...
September 27, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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