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Absence of SARM1 rescues development and survival of NMNAT2-deficient axons.
Gilley J, Orsomando G, Nascimento-Ferreira I, Coleman MP. Gilley J, et al. Cell Rep. 2015 Mar 31;10(12):1974-81. doi: 10.1016/j.celrep.2015.02.060. Epub 2015 Mar 26. Cell Rep. 2015. PMID: 25818290 Free PMC article.
Here, we show that NMNAT2 loss and resultant changes to NMNAT metabolites occur in injured SARM1-deficient axons despite their delayed degeneration and that axon degeneration specifically induced by NMNAT2 depletion requires SARM1. ...Furthermore, NAMPT inhib …
Here, we show that NMNAT2 loss and resultant changes to NMNAT metabolites occur in injured SARM1-deficient axons despite their delaye …
Protective effects of NAMPT or MAPK inhibitors and NaR on Wallerian degeneration of mammalian axons.
Alexandris AS, Ryu J, Rajbhandari L, Harlan R, McKenney J, Wang Y, Aja S, Graham D, Venkatesan A, Koliatsos VE. Alexandris AS, et al. Neurobiol Dis. 2022 Sep;171:105808. doi: 10.1016/j.nbd.2022.105808. Epub 2022 Jun 30. Neurobiol Dis. 2022. PMID: 35779777 Free PMC article.
Here we explored pharmacological strategies that modulate NMN and NAD(+) metabolism, namely the inhibition of the NMN-synthesizing enzyme NAMPT, activation of the nicotinic acid riboside (NaR) salvage pathway and inhibition of the NMNAT2-degrading DLK MAPK pathway i …
Here we explored pharmacological strategies that modulate NMN and NAD(+) metabolism, namely the inhibition of the NMN-synthesizing enzyme …
Regulation of NAD+/NADH Redox Involves the Protective Effects of Ginsenoside Rb1 against Oxygen-Glucose Deprivation/Reoxygenation-Induced Astrocyte Lesions.
Liu Y, Wang X, Xie J, Tang M. Liu Y, et al. Int J Mol Sci. 2023 Nov 7;24(22):16059. doi: 10.3390/ijms242216059. Int J Mol Sci. 2023. PMID: 38003249 Free PMC article.
Ginsenoside Rb1 also significantly increased the expression of NAMPT and NMNAT2, both of which are key players in NAD/NADH synthesis. ...
Ginsenoside Rb1 also significantly increased the expression of NAMPT and NMNAT2, both of which are key players in NAD/NADH syn …
Identification of the Nicotinamide Salvage Pathway as a New Toxification Route for Antimetabolites.
Buonvicino D, Mazzola F, Zamporlini F, Resta F, Ranieri G, Camaioni E, Muzzi M, Zecchi R, Pieraccini G, Dölle C, Calamante M, Bartolucci G, Ziegler M, Stecca B, Raffaelli N, Chiarugi A. Buonvicino D, et al. Cell Chem Biol. 2018 Apr 19;25(4):471-482.e7. doi: 10.1016/j.chembiol.2018.01.012. Epub 2018 Feb 22. Cell Chem Biol. 2018. PMID: 29478906 Free article.
Here, we report the identification of Vacor as a substrate metabolized by the consecutive action of NAMPT and NMNAT2 into the NAD analog Vacor adenine dinucleotide (VAD). This leads to inhibition of both enzymes, as well as NAD-dependent dehydrogenases, thereby caus …
Here, we report the identification of Vacor as a substrate metabolized by the consecutive action of NAMPT and NMNAT2 into the …
Aerobic and resistance exercise training reverses age-dependent decline in NAD+ salvage capacity in human skeletal muscle.
de Guia RM, Agerholm M, Nielsen TS, Consitt LA, Søgaard D, Helge JW, Larsen S, Brandauer J, Houmard JA, Treebak JT. de Guia RM, et al. Physiol Rep. 2019 Jul;7(12):e14139. doi: 10.14814/phy2.14139. Physiol Rep. 2019. PMID: 31207144 Free PMC article.
In skeletal muscle, NAD(+) is mainly generated by the NAD(+) salvage pathway in which nicotinamide phosphoribosyltransferase (NAMPT) is rate-limiting. NAMPT decreases with age in human skeletal muscle, and aerobic exercise training increases NAMPT levels in y …
In skeletal muscle, NAD(+) is mainly generated by the NAD(+) salvage pathway in which nicotinamide phosphoribosyltransferase (NAMPT) …
Activated NAD+ biosynthesis pathway induces olaparib resistance in BRCA1 knockout pancreatic cancer cells.
Sasaki Y, Inouchi T, Nakatsuka R, Inoue A, Masutani M, Nozaki T. Sasaki Y, et al. PLoS One. 2024 Apr 16;19(4):e0302130. doi: 10.1371/journal.pone.0302130. eCollection 2024. PLoS One. 2024. PMID: 38625917 Free PMC article.
Our results revealed activation of cell signaling pathway related to NAD+ metabolism in the olaparib-resistant C1/OLA cells, with increased expression of genes encoding the NAD+ biosynthetic enzymes NAMPT and NMNAT2. Moreover, intracellular NAD+ levels were signific …
Our results revealed activation of cell signaling pathway related to NAD+ metabolism in the olaparib-resistant C1/OLA cells, with increased …
Obesity Is Associated With Low NAD(+)/SIRT Pathway Expression in Adipose Tissue of BMI-Discordant Monozygotic Twins.
Jukarainen S, Heinonen S, Rämö JT, Rinnankoski-Tuikka R, Rappou E, Tummers M, Muniandy M, Hakkarainen A, Lundbom J, Lundbom N, Kaprio J, Rissanen A, Pirinen E, Pietiläinen KH. Jukarainen S, et al. J Clin Endocrinol Metab. 2016 Jan;101(1):275-83. doi: 10.1210/jc.2015-3095. Epub 2015 Nov 17. J Clin Endocrinol Metab. 2016. PMID: 26574954
MAIN OUTCOME MEASURES: Subcutaneous adipose tissue (SAT) transcriptomics was analyzed by using Affymetrix U133 Plus 2.0 chips, total SAT (poly-ADP) ribose polymerase (PARP) activity by an ELISA kit, body composition by dual-energy x-ray absorptiometry and magnetic resonance imagi …
MAIN OUTCOME MEASURES: Subcutaneous adipose tissue (SAT) transcriptomics was analyzed by using Affymetrix U133 Plus 2.0 chips, total SAT (po …
Nicotinic acid mononucleotide is an allosteric SARM1 inhibitor promoting axonal protection.
Sasaki Y, Zhu J, Shi Y, Gu W, Kobe B, Ve T, DiAntonio A, Milbrandt J. Sasaki Y, et al. Exp Neurol. 2021 Nov;345:113842. doi: 10.1016/j.expneurol.2021.113842. Epub 2021 Aug 14. Exp Neurol. 2021. PMID: 34403688 Free PMC article.
However, with injury or disease the levels of the NAD(+) biosynthetic enzyme NMNAT2 drop, increasing the NMN/ NAD(+) ratio and thereby promoting NMN binding to the SARM1 allosteric site, which in turn induces a conformational change activating the SARM1 NAD(+) hydrolase. . …
However, with injury or disease the levels of the NAD(+) biosynthetic enzyme NMNAT2 drop, increasing the NMN/ NAD(+) ratio and thereb …
A rise in NAD precursor nicotinamide mononucleotide (NMN) after injury promotes axon degeneration.
Di Stefano M, Nascimento-Ferreira I, Orsomando G, Mori V, Gilley J, Brown R, Janeckova L, Vargas ME, Worrell LA, Loreto A, Tickle J, Patrick J, Webster JR, Marangoni M, Carpi FM, Pucciarelli S, Rossi F, Meng W, Sagasti A, Ribchester RR, Magni G, Coleman MP, Conforti L. Di Stefano M, et al. Cell Death Differ. 2015 May;22(5):731-42. doi: 10.1038/cdd.2014.164. Epub 2014 Oct 17. Cell Death Differ. 2015. PMID: 25323584 Free PMC article.
Axons depend on the activity of the central enzyme in NAD biosynthesis, nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2), for their maintenance and degenerate rapidly when this activity is lost. ...NMN rises prior to degeneration and both the NAMPT inhibit …
Axons depend on the activity of the central enzyme in NAD biosynthesis, nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2), f …
Evaluation of the NAD+ biosynthetic pathway in ALS patients and effect of modulating NAD+ levels in hSOD1-linked ALS mouse models.
Harlan BA, Killoy KM, Pehar M, Liu L, Auwerx J, Vargas MR. Harlan BA, et al. Exp Neurol. 2020 May;327:113219. doi: 10.1016/j.expneurol.2020.113219. Epub 2020 Jan 31. Exp Neurol. 2020. PMID: 32014438 Free PMC article.
In addition, we found altered expression of enzymes involved in NAD(+) synthesis (NAMPT and NMNAT2) and decreased SIRT6 expression in the spinal cord of ALS patients, suggesting deficits of this neuroprotective pathway in the human pathology. ...
In addition, we found altered expression of enzymes involved in NAD(+) synthesis (NAMPT and NMNAT2) and decreased SIRT6 expres …