ライフサイエンスコーパス: NMN

1 NMN appeared to have stronger effects on liver fat catab

2 NMN binding triggers reorientation of the armadillo repe

3 NMN deamidase, a bacterial enzyme, shares NMN-consuming

4 NMN increased lifespan by normalizing NAD(+) redox imbal

5 NMN is a rate-limiting precursor for recycling to the es

6 NMN is a substrate of both ectoenzymes CD38 and CD73, wi

7 NMN supplementation up-regulated the expression of plate

8 NMN synthesis by NAMPT is powerfully inhibited by both N

9 NMN up-regulated alpha-ketoglutarate (KG) levels in Nduf

10 NMN-D alters the NAD(+) metabolic flux by lowering NMN,

11 ng IBC, thiamine, N(1)-methylnicotinamide (1-NMN), creatinine, carnitine, and metformin, which is a p

12 rt a pro-degenerative effect of accumulating NMN in axons in vivo.

13 ntral domain has a weak adenylyltransferase (NMN-AT; EC 2.7.7.1) activity that converts NMN directly

14 ate of orally and intravenously administered NMN and NR in mice using NAD(+) metabolomics.

15 Moreover, intravenously administered NMN and NR were rapidly degraded into nicotinamide and s

16 only a small portion of orally administered NMN and NR was directly absorbed from the small intestin

17 target of rapamycin (mTOR)] increased after NMN supplementation but did not change after placebo tre

18 modulate NMNH:NMN(+) ratio together with an NMN(+)-specific glucose dehydrogenase (GDH Ortho).

19 d HEK 293T cells; they lack constitutive and NMN-induced NADase activity; and they fail to promote ax

20 deficits, we compared treadmill exercise and NMN injection in offspring of obese mothers.

21 of NA phosphoribosyltransferase (NAPRT) and NMN adenyltransferase (NMNAT) 3.

22 production in neurons through an NMNAT2 and NMN dependent mechanism.

23 ate-limiting for the use of exogenous NR and NMN for NAD(+) synthesis.

24 NR and NMN require large dosages for effect.

25 Comparisons with NR and NMN show that in every instance, NRH provides greater NA

26 Inhibition is observed with reduced beta-NMN and alpha-NADH, but neither is as effective as beta-

27 select for increased discrimination between NMN and NMNH.

28 to be a bifunctional enzyme possessing both NMN adenylytransferase (NMNAT; EC ) and ribosylnicotinam

29 strate specificity of the enzyme toward both NMN and NaMN and reveal the structural mechanism for ade

30 nique dual substrate specificity toward both NMN and NaMN, thus flexible in participating in both de

31 The first step is catalyzed by NMN synthetase, which was identified and characterized i

32 systems and in Escherichia coli, enabled by NMN(H)'s distinct redox ratio firmly set by its designat

33 red NAD(+) and MgCl(2), and was inhibited by NMN and AMP, products of the ligase reaction.

34 The second step is performed by NMN adenylyltransferase of the NadM family.

35 lters an ATP-binding residue in the central (NMN-AT) domain.

36 table isotope-labelled compounds, we confirm NMN is metabolized extracellularly to NR that is then ta

37 (NMN-AT; EC 2.7.7.1) activity that converts NMN directly to NAD but is physiologically irrelevant.

38 nslated onto six different enzymes to create NMN(H)-orthogonal biocatalysts with a consistent ~10(3)-

39 op a phosphite dehydrogenase (PTDH) to cycle NMN(+) with ~147-fold improved catalytic efficiency, whi

40 a newly generated prokaryotic NMN-Deamidase (NMN-D) preserves severed axons for months and keeps them

41 (NMN) in zebrafish and mice, which decreases NMN levels by converting it to NaMN, protects against ax

42 This eliminates NMN-AT activity and places the enzyme in its default (DN

43 Unlike other yeast NMNATs, Pof1 exhibits NMN-specific adenylyltransferase activity.

44 D38 impairs, the conversion of extracellular NMN to NR as a precursor for intracellular NAD(+) biosyn

45 an cells require conversion of extracellular NMN to NR for cellular uptake and NAD(+) synthesis, expl

46 reated cells supplemented with extracellular NMN was strongly reduced in tumor cells, upon pharmacolo

47 Finally, NMN-D delays neurodegeneration caused by loss of the sol

48 The kcat for NMN+ was 5-fold higher than that of NAD+ and has the gre

49 N aptamer sequences was used to reselect for NMN binding.

50 Our results reveal a critical role for NMN in neurodegeneration in the fly, which extends beyon

51 as identified that increases specificity for NMN.

52 a phase transition reduces the threshold for NMN-based SARM1 activation to physiologically relevant l

53 (Nmnat2) catalyzes the synthesis of NAD from NMN and ATP.

54 In route 1, nicotinamide is removed from NMN in the periplasm and enters the cell as the free bas

55 2, described here, phosphate is removed from NMN in the periplasm by acid phosphatase (AphA), and the

56 This translocation furnishes NMN to replenish NAD(+) to compensate for the activation

57 er catalyst" that more efficiently generates NMN.

58 validation of the predicted route (NaMN --> NMN --> NAD) in F. tularensis including mathematical mod

59 y in pnuC* transporter mutants, which import NMN intact and can therefore grow on lower levels of NMN

60 Increased NMN synthesis by the expression of mouse nicotinamide ph

61 metabolic sensor responding to an increased NMN/NAD(+) ratio by cleaving residual NAD(+), thereby in

62 cleus and thereby sustain the stress-induced NMN/NAD(+) salvage pathway.

63 Hepatic NMNAT1 loss inhibited NMN-protected ALD.

64 Internal NMN produced by either route 2 or route 3 is deamidated

65 ells with SBI-797812 increases intracellular NMN and NAD(+).

66 In mammals, keeping NMN levels low potently preserves axons after injury.

67 In contrast to other known NMN ATs, biophysical characterizations reveal it to be a

68 alters the NAD(+) metabolic flux by lowering NMN, while NAD(+) remains unchanged in vivo.

69 Here, we demonstrate that lowering NMN levels in Drosophila through the expression of a new

70 ammonium (TBuMA), and N'-methylnicotinamide (NMN).

71 cting stem-loops is proposed for the minimal NMN-binding RNA.

72 cterial nicotinamide adenine mononucleotide (NMN) in zebrafish and mice, which decreases NMN levels b

73 We established nicotinamide mononucleotide (NMN(+)) as a noncanonical cofactor orthogonal to NAD(P)(

74 (NCBs) such as nicotinamide mononucleotide (NMN(+)) provide enhanced scalability for biomanufacturin

75 nical cofactor, nicotinamide mononucleotide (NMN(+)).

76 Nicotinamide mononucleotide (NMN) adenylyltransferase 2 (Nmnat2) catalyzes the synthe

77 levels through nicotinamide mononucleotide (NMN) administration prevented cisplatin-induced abnormal

78 le synthesis of nicotinamide mononucleotide (NMN) and inorganic pyrophosphate (PP i) from nicotinamid

79 ccumulations of nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) in the amidated salv

80 ursors, such as nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), exhibits beneficial

81 (+) precursors, nicotinamide mononucleotide (NMN) and NR, can reverse the FK866-induced cell death, t

82 Nicotinamide mononucleotide (NMN) availability is a rate-limiting factor in mammalian

83 th NaMN and the nicotinamide mononucleotide (NMN) but shows specificity for the nicotinate.

84 from exogenous nicotinamide mononucleotide (NMN) by three routes.

85 D(+) precursor, nicotinamide mononucleotide (NMN) can reverse some of the negative consequences of hi

86 N) and mediates nicotinamide mononucleotide (NMN) catabolism, thereby contributing to both NmR salvag

87 increase in the nicotinamide mononucleotide (NMN) concentration, which leads to the allosteric activa

88 D(+) precursor, nicotinamide mononucleotide (NMN) extended lifespan of Ndufs4-KO mice and attenuated

89 osphorolysis of nicotinamide mononucleotide (NMN) from kinetic isotope effects (KIEs).

90 n (Rb) and beta-nicotinamide mononucleotide (NMN) have been isolated by in vitro selection.

91 AD(+) precursor nicotinamide mononucleotide (NMN) increases BubR1 abundance in vivo.

92 Nicotinamide mononucleotide (NMN) is a widely investigated metabolic precursor to the

93 cleoside of the nicotinamide mononucleotide (NMN) leaving group are oriented solely via atomic intera

94 tion of NaMN to nicotinamide mononucleotide (NMN) occurs before the adenylylation reaction, which con

95 ursors, such as nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR), protects against met

96 by olaparib or nicotinamide mononucleotide (NMN) supplementation rescued NAD(+) levels and alleviate

97 which converts nicotinamide mononucleotide (NMN) to NAD(+), activates SARM1 via an unknown mechanism

98 Since nicotinamide mononucleotide (NMN) was reported to restore NAD(+) levels, we next inve

99 The addition of nicotinamide mononucleotide (NMN), a byproduct of NAMPT that restores NAD concentrati

100 treatment with nicotinamide mononucleotide (NMN), a NAD(+)-boosting compound.

101 bio-precursor, nicotinamide mononucleotide (NMN), from tumor microenvironments, thereby enhancing tu

102 the presence of nicotinamide mononucleotide (NMN), its physiological activator.

103 e production of nicotinamide mononucleotide (NMN), the predominant NAD(+) precursor in mammalian cell

104 boside (NR) and nicotinamide mononucleotide (NMN), the presence of multiple cellular compartments tha

105 zymatic product nicotinamide mononucleotide (NMN), was not blocked by the Nampt enzyme inhibitor FK86

106 treatment with nicotinamide mononucleotide (NMN), which bypasses the block in NAD(+) synthesis induc

107 an alternative nicotinamide mononucleotide (NMN)-preferring adenylyltransferase (slr0787 gene).

108 action product, nicotinamide mononucleotide (NMN).

109 AD(+) precursor nicotinamide mononucleotide (NMN).

110 teric activator nicotinamide mononucleotide (NMN).

111 boside (NR) and nicotinamide mononucleotide (NMN).

112 cotinamide into nicotinamide mononucleotide (NMN).

113 t internally to nicotinamide mononucleotide (NMN).

114 Nicotinamide/nicotinate mononucleotide (NMN/ NaMN)adenylyltransferase (NMNAT) is an indispensabl

115 the condensation of pyridine mononucleotide (NMN or NaMN) with the AMP moiety of ATP to form NAD (or

116 by the organic cation n-methyl-nicotinamide (NMN), being instead stimulated by it (fourfold).

117 non-deamidating utilization of nicotinamide (NMN shunt).

118 Like overexpressed NMNATs, NMN deamidase reduces NMN accumulation in injured mouse

119 that completes the toolkit to modulate NMNH:NMN(+) ratio together with an NMN(+)-specific glucose de

120 NAM (900 mg/kg) significantly increased NR, NMN, ADPR, NAM, and m-NAM levels.

121 was downregulated and so the accumulation of NMN and NR was best explained by reduced flux through th

122 d primarily by the ADP moiety; no binding of NMN or nicotinamide is observed by ITC.

123 double-blind trial to evaluate the effect of NMN supplementation on metabolic function in postmenopau

124 ct and can therefore grow on lower levels of NMN.

125 However, the in vivo metabolic pathways of NMN and NR remain to be elucidated.

126 ve ATPase activity, allows the production of NMN at product:substrate ratios thermodynamically forbid

127 is activated by an increase in the ratio of NMN to NAD(+) and show that both metabolites compete for

128 further study to confirm the suitability of NMN for use in reversing metabolic dysfunction linked to

129 strates and NAD(+), and the IC(50) values of NMN and AMP, examined the effects of MgCl(2) and PEG(800

130 CD38 can mediate a base-exchange reaction on NMN, whereby the nicotinamide ring is exchanged with a f

131 reversal of these outcomes through NAD(+) or NMN supplementation was independent of CD73.

132 ular NAD(+) when supplemented with NAD(+) or NMN.

133 ere given treadmill exercise for 9 weeks, or NMN injection daily for 18 days.

134 This is based on an orthogonal, NMN(+)-dependent glycolytic pathway in Escherichia coli

135 rom their precursors, 4'-phosphopantetheine, NMN, and FMN, respectively.

136 recombinant human CD73 only poorly processes NMN but not NAD(+).

137 expression of a newly generated prokaryotic NMN-Deamidase (NMN-D) preserves severed axons for months

138 sent the development of Nox Ortho, a reduced NMN(+) (NMNH)-specific oxidase, that completes the toolk

139 procal enzyme to recycle the ensuing reduced NMN(+).

140 chia coli to exclusively rely on the reduced NMN(+) (NMNH).

141 overexpressed NMNATs, NMN deamidase reduces NMN accumulation in injured mouse sciatic nerves and pre

142 The potent neuroprotection by reducing NMN levels is similar to the interference with other ess

143 Remarkably, NMN deamidase also rescues axonal outgrowth and perinata

144 NMN deamidase, a bacterial enzyme, shares NMN-consuming activity with NMNAT2, but not NAD-synthesi

145 neurodegeneration caused by loss of the sole NMN-consuming and NAD(+)-synthesizing enzyme dNmnat.

146 l by maintaining low levels of its substrate NMN rather than generating NAD; however, this is still d

147 Noncyclizable substrates NMN+ and nicotinamide-7-deaza-hypoxanthine dinucleotide

148 complex of CD38 with one of its substrates, NMN, showed that the nicotinamide moiety was in close co

149 With the natural substrates, NMN and pyrophosphate (PPi), the intrinsic KIEs of [1'-(

150 These results demonstrate that NMN increases muscle insulin sensitivity, insulin signal

151 f SARM1 and demonstrate via mutagenesis that NMN binding is required for injury-induced SARM1 activat

152 Here we show that NMN deamidase can also delay axon degeneration in zebraf

153 We show that NMN influences the structure of SARM1 and demonstrate vi

154 We also show that NMN-induced activation of dSarm mediates axon degenerati

155 These findings showed that NMN and NR are indirectly converted to NAD(+) via unexpe

156 The NMN deamidase mouse will be an important tool to further

157 l molecule inhibition of CD38 abolishing the NMN-induced increase in NaMN and nicotinic acid adenine

158 14); (ii) comprise the interface between the NMN-binding domain (domain Ia) and the nucleotidyltransf

159 liquid-to-solid phase transition lowers the NMN concentration required to activate the catalytic act

160 A mutagenized pool based on one of the NMN aptamer sequences was used to reselect for NMN bindi

161 Together with the crystal structure of the NMN.PPi.Mg2.enzyme complex, the reaction coordinate is d

162 itors with oxacarbenium mimics replacing the NMN-ribosyl group of NAD(+) show 200-620-fold increased

163 gh frequency stimulation (100 Hz), while the NMN-treated cKO mice responded similarly to the control

164 Increasing NAD(+) through NMN supplementation offers a potential therapeutic strat

165 Internal NmR is then converted back to NMN by the NmR kinase activity of NadR.

166 structures of the SARM1 ARM domain bound to NMN and of the homo-octameric SARM1 complex in the absen

167 With ATP hydrolysis coupled to NMN synthesis, the catalytic efficiency of the system is

168 owed cell-type specific responses of CSMN to NMN treatment to be assessed in vitro.

169 ofactor specificity switch from NAD(P)(+) to NMN(+).

170 M), and the K eq shifts -2.1 kcal/mol toward NMN formation.

171 hifts the NAMPT reaction equilibrium towards NMN formation, increases NAMPT affinity for ATP, stabili

172 e catalytic domain is flanked by an upstream NMN-binding module and by downstream OB-fold, zinc finge

173 ection platform to evolve enzymes to utilize NMN(+)-based reducing power.

174 To investigate whether NMN can impact developmentally-set metabolic deficits, w

175 NAD(+) levels, we next investigated whether NMN treatment would improve the health of diseased corti

176 However, it remains unclear whether NMN is also a key mediator of axon degeneration and dSar

177 tochondrial morphology in the cKO mice, with NMN treatment restoring sarcomere alignment but not mito

178 When the cKO mice were treated with NMN, vesicle endocytosis/exocytosis was improved and end