A rise in NAD precursor nicotinamide mononucleotide (NMN) after injury promotes axon degeneration
Open accessAbstract
NAD metabolism regulates diverse biological processes, including ageing, circadian rhythm and axon survival. 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. However, whether axon survival is regulated by the supply of NAD or by another action of this enzyme remains unclear. Here we show that the nucleotide precursor of NAD, nicotinamide mononucleotide (NMN), accumulates after nerve injury and promotes axon degeneration. Inhibitors of NMN-synthesising enzyme NAMPT confer robust morphological and functional protection of injured axons and synapses despite lowering NAD. Exogenous NMN abolishes this protection, suggesting that NMN accumulation within axons after NMNAT2 degradation could promote degeneration. Ectopic expression of NMN deamidase, a bacterial NMN-scavenging enzyme, prolongs survival of injured axons, providing genetic evidence to support such a mechanism. NMN rises prior to degeneration and both the NAMPT inhibitor FK866 and the axon protective protein Wld(S) prevent this rise. These data indicate that the mechanism by which NMNAT and the related Wld(S) protein promote axon survival is by limiting NMN accumulation. They indicate a novel physiological function for NMN in mammals and reveal an unexpected link between new strategies for cancer chemotherapy and the treatment of axonopathies.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Most bacteria have a NAM deamidase, an enzyme that converts NAM into NA.
“Most bacteria have a NAM deamidase, an enzyme that converts NAM into NA.”
From Nicotinamide riboside and nicotinamide mononucleotide facilitate NAD <sup>+</sup> synthesis via enterohepatic circulation (2025) · cites this paper as [27]
The Results section (“Genetic data confirm that NMN and NAMPT are necessary for rapid Wallerian degeneration”; page unavailable) says many bacterial species have an NMN deamidase that converts NMN to NaMN. The claim instead names NAM deamidase, gives NAM to NA as its reaction, and says “most” rather than “many” bacteria. (LLM, conf=0.85)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredGut microbiota deamidase converts NAM, NR, NMN, and NAD+ to their deamidated forms.
“have deamidase, which converts NAM, NR, NMN, and NAD+ to their deamidated forms (26–28).”
From Nicotinamide riboside and nicotinamide mononucleotide facilitate NAD <sup>+</sup> synthesis via enterohepatic circulation (2025) · cites this paper as [27]
The Results section (‘Genetic data confirm that NMN and NAMPT are necessary for rapid Wallerian degeneration’; page not provided) says bacterial NMN deamidase converts NMN to NaMN. It does not identify the bacteria as gut microbiota or say that the deamidase converts NAM, NR, or NAD+ to deamidated forms. (LLM, conf=0.88)
Experimental — accuracy not yet measuredMammals do not have a homologous enzyme to NAM deamidase.
“However, mammals do not have a homologous enzyme (12, 25–28).”
From Nicotinamide riboside and nicotinamide mononucleotide facilitate NAD <sup>+</sup> synthesis via enterohepatic circulation (2025) · cites this paper as [27]
The Results section states that mammals lack an NMN deamidase, which converts nicotinamide mononucleotide (NMN) to NaMN. The claim concerns NAM (nicotinamide) deamidase, a different enzyme; searches for NAM deamidase and nicotinamidase found no passage addressing whether mammals have a homolog. (LLM, conf=0.76)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Imaging Neuronal Subsets in Transgenic Mice Expressing Multiple Spectral Variants of GFP
Feng, G., Mellor, R. H., Bernstein, M., Keller-Peck, C., Nguyen, Q. T., Wallace, M., Nerbonne, J. M., Lichtman, J. W., & Sanes, J. R. (2000) · Neuron · doi:10.1016/s0896-6273(00)00084-2 · Cited by 3,042 · see citing works
Gomes, A. P., Price, N. L., Ling, A. J. Y., Moslehi, J. J., Montgomery, M. K., Rajman, L., White, J. P., Teodoro, J. S., Wrann, C. D., Hubbard, B. P., et al. (2013) · Cell · doi:10.1016/j.cell.2013.11.037 · Cited by 1,482 · see citing works
Yoshino, J., Mills, K. F., Yoon, M. J., & Imai, S.-I. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.08.014 · Cited by 1,340 · see citing works
Increased Nuclear NAD Biosynthesis and SIRT1 Activation Prevent Axonal Degeneration
Araki, T., Sasaki, Y., & Milbrandt, J. (2004) · Science · doi:10.1126/science.1098014 · Cited by 1,060 · cited 1× · see citing works
“that NAD synthesis is central to its neuroprotective mechanism.(25,26) In contrast, our data show that NMNAT-”
BackgroundNAD+ metabolism in health and disease
Belenky, P. A., Bogan, K. L., & Brenner, C. (2006) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2006.11.006 · Cited by 984 · cited 3× · see citing works
“Their ability to protect cell bodies from long-term FK866 toxicity (Supplementary Figure S5) confirmed they had entered the cell and could be converted to NAD as long as NMNATactivity is present, as this enzyme is required to convert NaMN to NAD (see Figure 1a and Nikiforov et al.33 and Belenky et al.34).”
BackgroundAxon degeneration mechanisms: Commonality amid diversity
Coleman, M. (2005) · Nature reviews. Neuroscience · doi:10.1038/nrn1788 · Cited by 819 · cited 1× · see citing works
“Degeneration of continuous axons after axonal transport block in some neurodegenerative disorders is mechanistically related to Wallerian degeneration, as Wld blocks some of these too.(3,37) We tested whether FK866 and NMN also influence the Vincristine primary culture model of Wallerian-like degeneration, a pathology…”
BackgroundSelf-citationdSarm/Sarm1 Is Required for Activation of an Injury-Induced Axon Death Pathway
Osterloh, J. M., Yang, J. H., Rooney, T. M., Fox, A. N., Adalbert, R., Powell, E. H., Sheehan, A. E., Avery, M. A., Hackett, R., Logan, M. A., et al. (2012) · Science · doi:10.1126/science.1223899 · Cited by 688 · see citing works
Self-citationAxonal Self-Destruction and Neurodegeneration
Raff, M., Whitmore, A., & Finn, J. (2002) · Science · doi:10.1126/science.1068613 · Cited by 670 · cited 1× · see citing works
“Our results tie an NMN increase to axon degeneration, suggesting it could be the long hypothesized ‘deleterious factor’(55) and key player in the activemechanism of axon degeneration.(56,57) They identify pharmacological agents that delay axon degeneration and suggest an important potential for combinatorial cancer tr…”
Absence of Wallerian Degeneration does not Hinder Regeneration in Peripheral Nerve
Lunn, E. R., Perry, V. H., Brown, M. C., Rosen, H., & Gordon, S. (1989) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1989.tb00771.x · Cited by 646 · see citing works
Hasmann, M., & Schemainda, I. (2003) · PubMed · Cited by 618 · see citing works
Wallerian degeneration: an emerging axon death pathway linking injury and disease
Conforti, L., Gilley, J., & Coleman, M. P. (2014) · Nature reviews. Neuroscience · doi:10.1038/nrn3680 · Cited by 611 · cited 3× · see citing works
“Wld blocks axon degeneration in some disease models, indicating a mechanistic similarity.(3) Therefore understanding the pathway it influences is an excellent route towards novel therapeutic strategies.”
BackgroundSelf-citationWallerian degeneration of injured axons and synapses is delayed by a Ube4b/Nmnat chimeric gene
Mack, T. G. A., Reiner, M., Beirowski, B., Mi, W., Emanuelli, M., Wagner, D., Thomson, D., Gillingwater, T., Court, F., Conforti, L., et al. (2001) · Nature Neuroscience · doi:10.1038/nn770 · Cited by 611 · cited 1× · see citing works
“Wld is a modified nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) enzyme, whose N-terminal extension partially relocates NMNAT1 from nuclei to axons, conferring gain of function.(9,10) In mammals, three NMNAT isoforms, nuclear NMNAT1, cytoplasmic NMNAT2 and mitochondrial NMNAT3, catalyse nicotinamide adenin…”
BackgroundSelf-citationThe Drosophila Cell Corpse Engulfment Receptor Draper Mediates Glial Clearance of Severed Axons
MacDonald, J. M., Beach, M. G., Porpiglia, E., Sheehan, A. E., Watts, R. J., & Freeman, M. R. (2006) · Neuron · doi:10.1016/j.neuron.2006.04.028 · Cited by 523 · see citing works
Berger, F., Lau, C., Dahlmann, M., & Ziegler, M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m508660200 · Cited by 508 · cited 1× · see citing works
“In mammals, three NMNAT isoforms, nuclear NMNAT1, cytoplasmic NMNAT2 and mitochondrial NMNAT3, catalyse nicotinamide adenine dinucleotide (NAD) synthesis from nicotinamide mononucleotide (NMN) and adenosine triphosphate (ATP; Figure 1a).(11,12) Several reports indicate Wld protects injured axons by maintaining axonal…”
BackgroundWallerian Degeneration, Wld<sup>S</sup>, and Nmnat
Coleman, M. P., & Freeman, M. R. (2010) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-060909-153248 · Cited by 473 · see citing works
Self-citationEndogenous Nmnat2 Is an Essential Survival Factor for Maintenance of Healthy Axons
Gilley, J., & Coleman, M. P. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000300 · Cited by 472 · cited 12× · see citing works
“To exclude intracellular conversion of NMN to NAD, mediated by any residual axonal NMNAT2, we also added 1mM NMN to FK866-protected neurites 12 h after cutting, a time when little or no NMNAT2 remains.(16) Here, NMN restored axon degeneration within 3 h of addition (Figure 2d).”
BackgroundMethodResultInfluentialSelf-citationOn the degeneration of rat neuromuscular junctions after nerve section
Miledi, R., & Slater, C. R. (1970) · The Journal of Physiology · doi:10.1113/jphysiol.1970.sp009076 · Cited by 425 · see citing works
Belenky, P., Racette, F. G., Bogan, K. L., McClure, J. M., Smith, J. S., & Brenner, C. (2007) · Cell · doi:10.1016/j.cell.2007.03.024 · Cited by 411 · see citing works
Axon pathology in neurological disease: a neglected therapeutic target
Coleman, M. P., & Perry, V. H. (2002) · Trends in Neurosciences · doi:10.1016/s0166-2236(02)02255-5 · Cited by 383 · cited 1× · see citing works
“Our results tie an NMN increase to axon degeneration, suggesting it could be the long hypothesized ‘deleterious factor’(55) and key player in the activemechanism of axon degeneration.(56,57) They identify pharmacological agents that delay axon degeneration and suggest an important potential for combinatorial cancer tr…”
Self-citationStoll, G., Jander, S., & Myers, R. R. (2002) · Journal of the Peripheral Nervous System · doi:10.1046/j.1529-8027.2002.02002.x · Cited by 382 · cited 1× · see citing works
“Axon degeneration in disease shares features with the progressive breakdown of the distal segment of severed axons as described by Augustus Waller in 1850 and named Wallerian degeneration.(1) The serendipitous discovery of Wallerian degeneration slow (Wld) mice, where transected axons survive 10 times longer than in w…”
BackgroundA local mechanism mediates NAD-dependent protection of axon degeneration
Wang, J., Zhai, Q., Chen, Y., Lin, E., Gu, W., McBurney, M. W., & He, Z. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200504028 · Cited by 352 · cited 1× · see citing works
“that NAD synthesis is central to its neuroprotective mechanism.(25,26) In contrast, our data show that NMNAT-”
BackgroundPathways and Subcellular Compartmentation of NAD Biosynthesis in Human Cells
Nikiforov, A., Dölle, C., Niere, M., & Ziegler, M. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.213298 · Cited by 326 · cited 4× · see citing works
“Their ability to protect cell bodies from long-term FK866 toxicity (Supplementary Figure S5) confirmed they had entered the cell and could be converted to NAD as long as NMNATactivity is present, as this enzyme is required to convert NaMN to NAD (see Figure 1a and Nikiforov et al.33 and Belenky et al.34).”
BackgroundInfluentialWang, P., Xu, T., Guan, Y., Tian, W., Viollet, B., Rui, Y., Zhai, Q., Su, D., & Miao, C. (2011) · Annals of Neurology · doi:10.1002/ana.22236 · Cited by 288 · see citing works
Conforti, L., Tarlton, A., Mack, T. G. A., Mi, W., Buckmaster, E. A., Wagner, D., Perry, V. H., & Coleman, M. P. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.21.11377 · Cited by 251 · cited 1× · see citing works
“Wld is a modified nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) enzyme, whose N-terminal extension partially relocates NMNAT1 from nuclei to axons, conferring gain of function.(9,10) In mammals, three NMNAT isoforms, nuclear NMNAT1, cytoplasmic NMNAT2 and mitochondrial NMNAT3, catalyse nicotinamide adenin…”
BackgroundSelf-citationSasaki, Y., Vohra, B. P. S., Lund, F. E., & Milbrandt, J. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.5469-08.2009 · Cited by 243 · cited 2× · see citing works
“Although NMNAT activity is required for protection,(13) the hypothesis that increased NAD levels are responsible(25,26) does not fit some data.(27,28) While further investigating the role of NAD, we found that”
BackgroundMethodWatson, M., Roulston, A., Bélec, L., Billot, X., Marcellus, R., Bédard, D., Bernier, C., Branchaud, S., Chan, H., Dairi, K., et al. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00112-09 · Cited by 229 · see citing works
Axonal Degeneration Is Mediated by the Mitochondrial Permeability Transition Pore
Barrientos, S. A., Martínez, N. W., Yoo, S., Jara, J. S., Zamorano, S., Hetz, C. A., Twiss, J. L., Álvarez, J., & Court, F. A. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.4065-10.2011 · Cited by 207 · cited 2× · see citing works
“Inhibiting mitochondrial permeability transition pore protects degenerating axons.(24) However, Wld is”
BackgroundThe Highwire Ubiquitin Ligase Promotes Axonal Degeneration by Tuning Levels of Nmnat Protein
Xiong, X., Hao, Y., Sun, K., Li, J., Li, X., Mishra, B., Soppina, P., Wu, C., Hume, R. I., & Collins, C. A. (2012) · PLoS Biology · doi:10.1371/journal.pbio.1001440 · Cited by 200 · see citing works
Inhibition of Nicotinamide Phosphoribosyltransferase
Pittelli, M., Formentini, L., Faraco, G., Lapucci, A., Rapizzi, E., Cialdai, F., Romano, G., Moneti, G., Moroni, F., & Chiarugi, A. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.136739 · Cited by 189 · see citing works
Ribchester, R. R., Thomson, D., Wood, N. I., Hinks, T., Gillingwater, T. H., Wishart, T. M., Court, F. A., & Morton, A. J. (2004) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2004.03783.x · Cited by 165 · cited 1× · see citing works
“Intracellular recordings were made using standard microelectrode techniques as described previously.(61,62) The WinWCP (Strathclyde Electrophysiological Software, Glasgow, UK) and MiniAnalysis (Synaptosoft, Atlanta, GA, USA) softwares were used for EPP and mEPP(61) recording and analysis.”
MethodSelf-citationThe Phr1 ubiquitin ligase promotes injury-induced axon self-destruction
Babetto, E., Beirowski, B., Russler, E. V., Milbrandt, J., & Diantonio, A. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.04.013 · Cited by 159 · see citing works
Yahata, N., Yuasa, S., & Araki, T. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.4304-08.2009 · Cited by 154 · see citing works
WldS requires Nmnat1 enzymatic activity and N16–VCP interactions to suppress Wallerian degeneration
Avery, M. A., Sheehan, A. E., Kerr, K. S., Wang, J., & Freeman, M. R. (2009) · The Journal of Cell Biology · doi:10.1083/jcb.200808042 · Cited by 140 · see citing works
Conforti, L., Fang, G., Beirowski, B., Wang, M. S., Sorci, L., Asress, S., Adalbert, R., Silva, A., Bridge, K., Huang, X. P., et al. (2006) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401944 · Cited by 136 · cited 4× · see citing works
“coli NMN deamidase, fused to enhanced green fluorescent protein (EGFP), into SCG neurons (Figure 3b) and found a robust delay in the degeneration of transected neurites (Figures 3c and d), stronger than the effect of FK866 and similar to that of Wld.(27) Mutations that greatly reduce catalytic activity (Figure 3a) cau…”
BackgroundMethodResultInfluentialSelf-citationCompartmentation of NAD+‐dependent signalling
Koch‐Nolte, F., Fischer, S., Haag, F., & Ziegler, M. (2011) · FEBS Letters · doi:10.1016/j.febslet.2011.03.045 · Cited by 124 · cited 1× · see citing works
“In mammals, three NMNAT isoforms, nuclear NMNAT1, cytoplasmic NMNAT2 and mitochondrial NMNAT3, catalyse nicotinamide adenine dinucleotide (NAD) synthesis from nicotinamide mononucleotide (NMN) and adenosine triphosphate (ATP; Figure 1a).(11,12) Several reports indicate Wld protects injured axons by maintaining axonal…”
BackgroundMilde, S., Gilley, J., & Coleman, M. P. (2013) · PLoS Biology · doi:10.1371/journal.pbio.1001539 · Cited by 124 · cited 1× · see citing works
“These data support the notion that NMNAT2 rapidly degrades in injured axons and that Wld directly substitutes for it when present.(16,19) The early rise in NMN suggests that NMNAT2 is depleted after axotomy in vivo as well as in primary culture,(16,19) although possibly less quickly consistent with the slower onset of…”
ResultSelf-citationRescue of Peripheral and CNS Axon Defects in Mice Lacking NMNAT2
Gilley, J., Adalbert, R., Yu, G., & Coleman, M. P. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.1534-13.2013 · Cited by 123 · cited 2× · see citing works
“5 embryos of heterozygous (+/gtE) or homozygous (gtE/gtE) for the Nmnat2 allele from which NMNAT2 expression is non-detectable.(18) There is a clear increase in NMN levels in homozygous mice that do not express any NMNAT2 (n= 5, one-way ANOVA with Tukey’s post-hoc test, ***Po0.”
BackgroundMethodSelf-citationAnticancer agent CHS-828 inhibits cellular synthesis of NAD
Olesen, U. H., Christensen, M. K., Björkling, F., Jäättelä, M., Jensen, P. B., Sehested, M., & Nielsen, S. J. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.01.019 · Cited by 122 · cited 1× · see citing works
“Here, by investigating the action of Wld, we observed that FK866 and CHS-828, two drugs already in human clinical trials for cancer, are axon protective.(29,53) We confirm significant protection of neuromuscular synapses, potentiation of Wld phenotype in organotypic nerve/muscle explants and prevention of Vincristine-…”
BackgroundBeirowski, B., Berek, L., Adalbert, R., Wagner, D. A., Grumme, D., Addicks, K., Ribchester, R. R., & Coleman, M. P. (2003) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2003.10.016 · Cited by 122 · see citing works
Self-citationChemotherapy-induced neurotoxicity: the value of neuroprotective strategies.
Beijers, A. J. M., Jongen, J. L. M., & Vreugdenhil, G. (2012) · PubMed · Cited by 120 · see citing works
WldS protein requires Nmnat activity and a short N-terminal sequence to protect axons in mice
Conforti, L., Wilbrey, A. L., Morreale, G., Janečková, L., Beirowski, B., Adalbert, R., Mazzola, F., Stefano, M. D., Hartley, R., Babetto, E., et al. (2009) · The Journal of Cell Biology · doi:10.1083/jcb.200807175 · Cited by 113 · see citing works
Self-citationNon-Nuclear Wld S Determines Its Neuroprotective Efficacy for Axons and Synapses In Vivo
Beirowski, B., Babetto, E., Gilley, J., Mazzola, F., Conforti, L., Janečková, L., Magni, G., Ribchester, R. R., & Coleman, M. P. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.3814-08.2009 · Cited by 98 · see citing works
Self-citationMartin, S. M., O’Brien, G. S., Portera‐Cailliau, C., & Sagasti, A. (2010) · Development · doi:10.1242/dev.053611 · Cited by 98 · see citing works
Self-citationCharacterization of NAD Uptake in Mammalian Cells
Billington, R. A., Travelli, C., Ercolano, E., Galli, U., Roman, C. B., Grolla, A. A., Canonico, P. L., Condorelli, F., & Genazzani, A. A. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m706204200 · Cited by 97 · see citing works
Garavaglia, S., Bruzzone, S., Cassani, C., Canella, L., Allegrone, G., Sturla, L., Mannino, E., Millo, E., De Flora, A., & Rizzi, M. (2012) · Biochemical Journal · doi:10.1042/bj20111263 · Cited by 94 · see citing works
Gillingwater, T. H., Thomson, D., Mack, T. G. A., Soffin, E. M., Mattison, R. J., Coleman, M. P., & Ribchester, R. R. (2002) · The Journal of Physiology · doi:10.1113/jphysiol.2002.022343 · Cited by 91 · see citing works
Self-citationAdalbert, R., Gillingwater, T. H., Haley, J. E., Bridge, K., Beirowski, B., Berek, L., Wagner, D. A., Grumme, D., Thomson, D., Çelik, A., et al. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2004.03833.x · Cited by 86 · see citing works
Self-citationHicks, A. N., Lorenzetti, D., Gilley, J., Lu, B., Andersson, K., Milligan, C., Overbeek, P. A., Oppenheim, R. W., & Bishop, C. E. (2012) · PLoS ONE · doi:10.1371/journal.pone.0047869 · Cited by 85 · see citing works
Self-citationAssay methods for nicotinamide mononucleotide adenylyltransferase of wide applicability.
Balducci, E., Emanuelli, M., Raffaelli, N., Ruggieri, S., Amici, A., Magni, G., Orsomando, G., Polzonetti, V., & Natalini, P. (1995) · Analytical Biochemistry · doi:10.1006/abio.1995.1315 · Cited by 79 · cited 2× · see citing works
“After 30 min incubation at 37 °C, the formed NaAD was quantified by an HPLC-based method.(60)”
MethodSelf-citationThe gene for slow Wallerian degeneration (Wld(s)) is also protective against vincristine neuropathy.
Wang, M.-S., Wu, Y., Culver, D. G., & Glass, J. (2001) · Neurobiology of Disease · doi:10.1006/nbdi.2000.0334 · Cited by 77 · see citing works
NAD depletion by FK866 induces autophagy
Billington, R. A., Genazzani, A. A., Travelli, C., & Condorelli, F. (2008) · Autophagy · doi:10.4161/auto.5635 · Cited by 77 · see citing works
Detection and pharmacological modulation of nicotinamide mononucleotide (NMN) in vitro and in vivo
Formentini, L., Moroni, F., & Chiarugi, A. (2009) · Biochemical Pharmacology · doi:10.1016/j.bcp.2009.02.017 · Cited by 76 · see citing works
Kitay, B. M., McCormack, R., Wang, Y., Tsoulfas, P., & Zhai, R. G. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt009 · Cited by 73 · see citing works
A Model of Toxic Neuropathy inDrosophilaReveals a Role for MORN4 in Promoting Axonal Degeneration
Bhattacharya, M. R. C., Gerdts, J., Naylor, S. A., Royse, E. X., Ebstein, S. Y., Sasaki, Y., Milbrandt, J., & DiAntonio, A. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.4951-11.2012 · Cited by 70 · cited 1× · see citing works
“Taxol-induced degeneration.(51) Due to structural homology, inhibition of NAD-dependent enzymes by NMN is another possibility, although NAD remains in a high molar excess over NMN.”
BackgroundGaleazzi, L., Bocci, P., Amici, A., Brunetti, L., Ruggieri, S., Romine, M., Reed, S., Osterman, A. L., Rodionov, D. A., Sorci, L., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.275818 · Cited by 67 · cited 1× · see citing works
“This enzyme converts NMN to NaMN (Figure 1a) and was recently identified and characterized in two bacterial species.(39) When ectopically expressed in HEK293T or PC12 cells, Escherichia coli NMN deamidase (kindly supplied by Professor Nadia Raffaelli) retains its enzyme activity and promptly converts NMN to NaMN (Figu…”
BackgroundBuckmaster, E. A., Perry, V. H., & Brown, M. C. (1995) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1995.tb01155.x · Cited by 61 · cited 1× · see citing works
“SCG and DRG explants were dissected and cultured, and axons were transected as previously described.(59) Neurites were allowed to extend for 5–7 days in all cultures before cut.”
MethodNatera-Naranjo, O., Kar, A. N., Aschrafi, A., Gervasi, N. M., MacGibeny, M., Gioio, A. E., & Kaplan, B. B. (2012) · Molecular and cellular neurosciences · doi:10.1016/j.mcn.2011.12.006 · Cited by 59 · see citing works
Bi, J., Li, H., Ye, S. Q., & Ding, S. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07566.x · Cited by 51 · cited 1× · see citing works
“15min after systemic administration, before falling back to normal levels as NAD rose,(48) and in ischemic models exogenous NAD was also protective.(46) In contrast, lesioned”
BackgroundRibchester, R. R., Tsao, J. W., Barry, J. A., Asgari‐Jirhandeh, N., Perry, V. H., & Brown, M. C. (1995) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1995.tb01159.x · Cited by 50 · cited 1× · see citing works
“Intracellular recordings were made using standard microelectrode techniques as described previously.(61,62) The WinWCP (Strathclyde Electrophysiological Software, Glasgow, UK) and MiniAnalysis (Synaptosoft, Atlanta, GA, USA) softwares were used for EPP and mEPP(61) recording and analysis.”
MethodSelf-citationO’Brien, G. S., Martin, S. M., Söllner, C., Wright, G. J., Becker, C. G., Portera‐Cailliau, C., & Sagasti, A. (2009) · Current Biology · doi:10.1016/j.cub.2009.10.051 · Cited by 49 · cited 1× · see citing works
“01% tricaine and mounted in 1% low melt agarose, and two-photon laser axotomy was carried out as previously described.(63) Time-lapse images were obtained at 20–25 min intervals from 12 to 20 h using a Zeiss LSM 510 confocal microscope.”
MethodSelf-citationVincent, A. J., Briggs, L., Chatwin, G. F. J., Emery, E., Tomlins, R., Oswald, M. C. W., Middleton, C. A., Evans, G. J., Sweeney, S. T., & Elliott, C. J. H. (2012) · Human Molecular Genetics · doi:10.1093/hmg/ddr609 · Cited by 49 · see citing works
Maintaining energy homeostasis is an essential component of WldS-mediated axon protection
Shen, H., Hyrc, K. L., & Goldberg, M. P. (2013) · Neurobiology of Disease · doi:10.1016/j.nbd.2013.07.007 · Cited by 35 · see citing works
Avery, M., Rooney, T., Pandya, J. D., Wishart, T., Gillingwater, T., Geddes, J. W., Sullivan, P., & Freeman, M. (2012) · Current Biology · doi:10.1016/j.cub.2012.02.043 · Cited by 13 · see citing works
APCI1307K Mutations and Forkhead Box Gene (FOXO1A): Another Piece of an Interesting Correlation
Agostini, M., Bedin, C., Pucciarelli, S., Enzo, M. V., Briarava, M., Seraglia, R., Ragazzi, E., Traldi, P., Molin, L., Urso, E. D. L., et al. (2012) · The International Journal of Biological Markers · doi:10.5301/jbm.2011.8908 · Cited by 5 · cited 1× · see citing works
“The serendipitous discovery of Wallerian degeneration slow (Wld) mice, where transected axons survive 10 times longer than in wild types (WTs),(2) suggested that axon degeneration is a regulated process, akin to apoptosis of the cell bodies but distinct in molecular terms.(3,4) This process appears conserved in rats,…”
BackgroundSelf-citation
Flagged first, then by citations
Cited by
Sorted by citations
NAD+ metabolism and its roles in cellular processes during ageing
Covarrubias, A. J., Perrone, R., Grozio, A., & Verdin, E. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00313-x · Cited by 1,617 · see citing works
Fricker, M., Tolkovsky, A. M., Borutaitė, V., Coleman, M. P., & Brown, G. C. (2018) · Physiological Reviews · doi:10.1152/physrev.00011.2017 · Cited by 1,122 · see citing works
“The decline in NAD (706) appears to be neither sufficient nor necessary, so current models include a rise in its precursor NMN (170), another metabolite yet to be identified (596), or a combination.”
Self-citationNAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR
Yoshino, J., Baur, J. A., & Imai, S.-I. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.11.002 · Cited by 1,061 · see citing works
NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential
Xie, N., Zhang, L., Gao, W. Q., Huang, C., Huber, P., Zhou, X., Li, C. L., Shen, G., & Zou, B. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00311-7 · Cited by 1,078 · see citing works
“The protection effect can also be abolished by the expression of exogenous NMN and ectopic expression of NMN deamidase.(489,496) Thirdly, NMNAT1 does not change the NAD biosynthesis, but prevents the SARM1-dependent NAD depletion caused by injury, which is important for axon degeneration.”
BackgroundTherapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence
Rajman, L., Chwalek, K., & Sinclair, D. A. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.02.011 · Cited by 865 · see citing works
“There is some evidence indicating that NMN treatment promotes axon degeneration and that the dependence on NMNAT2 for axon survival is due to its consumption of NMN rather than its NAD synthesis activity (Di Stefano et al., 2015).”
Vitamin B <sub>3</sub> modulates mitochondrial vulnerability and prevents glaucoma in aged mice
Williams, P. A., Harder, J. M., Foxworth, N. E., Cochran, K. E., Philip, V. M., Porciatti, V., Smithies, O., & John, S. W. M. (2017) · Science · doi:10.1126/science.aal0092 · Cited by 617 · see citing works
NAD+ homeostasis in health and disease
Katsyuba, E., Romani, M., Hofer, D., & Auwerx, J. (2020) · Nature Metabolism · doi:10.1038/s42255-019-0161-5 · Cited by 627 · see citing works
Programmed axon degeneration: from mouse to mechanism to medicine
Coleman, M. P., & Höke, A. (2020) · Nature reviews. Neuroscience · doi:10.1038/s41583-020-0269-3 · Cited by 320 · see citing works
Self-citationSARM1 is a metabolic sensor activated by an increased NMN/NAD+ ratio to trigger axon degeneration
Figley, M. D., Gu, W., Nanson, J. D., Shi, Y., Sasaki, Y., Cunnea, K., Malde, A. K., Jia, X., Luo, Z., Saikot, F. K., et al. (2021) · Neuron · doi:10.1016/j.neuron.2021.02.009 · Cited by 324 · see citing works
Axon Self-Destruction: New Links among SARM1, MAPKs, and NAD+ Metabolism
Gerdts, J., Summers, D. W., Milbrandt, J., & DiAntonio, A. (2016) · Neuron · doi:10.1016/j.neuron.2015.12.023 · Cited by 318 · see citing works
Traumatic Axonal Injury: Mechanisms and Translational Opportunities
Hill, C., Coleman, M., & Menon, D. (2016) · Trends in Neurosciences · doi:10.1016/j.tins.2016.03.002 · Cited by 312 · see citing works
“It has been proposed that it is NMN that may ultimately lead to the triggering of WD [57].”
BackgroundSelf-citationBrown, K. D., Maqsood, S., Huang, J.-Y., Pan, Y., Harkcom, W., Li, W., Sauve, A., Verdin, E., & Jaffrey, S. R. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.11.003 · Cited by 277 · see citing works
“However, in addition to the loss of the protective effects of NAD+, loss of NMNAT-2 could lead to the accumulation of NAD+ metabolic precursors that may have their own, potentially toxic, effects in axons (Di Stefano et al., 2014).”
The Axon-Myelin Unit in Development and Degenerative Disease
Stassart, R. M., Möbius, W., Nave, K.-A., & Edgar, J. M. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00467 · Cited by 246 · see citing works
Nicotinamide Riboside—The Current State of Research and Therapeutic Uses
Mehmel, M., Jovanović, N. D., & Spitz, U. P. (2020) · Nutrients · doi:10.3390/nu12061616 · Cited by 225 · see citing works
“Although NA and NAM can enter the NAD+ salvage pathway, several preclinical studies have confirmed that both NA and NAM can cause painful flushing sensations at therapeutic doses or other toxic effects [14,165,166].”
BackgroundTribble, J. R., Otmani, A., Sun, S., Ellis, S. A., Cimaglia, G., Vohra, R., Jöe, M., Lardner, E., Venkataraman, A. P., Domínguez‐Vicent, A., et al. (2021) · Redox Biology · doi:10.1016/j.redox.2021.101988 · Cited by 233 · see citing works
Nicotinamide mononucleotide (NMN) as an anti-aging health product – Promises and safety concerns
Nadeeshani, H., Li, J., Ying, T., Zhang, B., & Lu, J. (2021) · Journal of Advanced Research · doi:10.1016/j.jare.2021.08.003 · Cited by 213 · see citing works
“[78], inhibitors of NMN synthesising enzyme (NAMPT), provided robust functional and morphological protection of injured synapses and axons, regardless of reducing NAD.”
BackgroundNMNAT1 inhibits axon degeneration via blockade of SARM1-mediated NAD+ depletion
Sasaki, Y., Nakagawa, T., Mao, X., DiAntonio, A., & Milbrandt, J. (2016) · eLife · doi:10.7554/elife.19749 · Cited by 192 · see citing works
A Mechanistic Understanding of Axon Degeneration in Chemotherapy-Induced Peripheral Neuropathy
Fukuda, Y., Li, Y., & Segal, R. A. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00481 · Cited by 206 · see citing works
“Whether SARM1 alters NAD + or NMN to induce axon degeneration is an area of active investigation (Di Stefano et al., 2015, 2017; Gerdts et al., 2015; Sasaki et al., 2016; Essuman et al., 2017).”
BackgroundThe NAD+-mediated self-inhibition mechanism of pro-neurodegenerative SARM1
Jiang, Y., Liu, T., Lee, C., Chang, Q., Yang, J. H., & Zhang, Z. (2020) · Nature · doi:10.1038/s41586-020-2862-z · Cited by 199 · see citing works
The Influence of Nicotinamide on Health and Disease in the Central Nervous System
Fricker, R. A., Green, E. L., Jenkins, S. I., & Griffin, S. M. (2018) · International Journal of Tryptophan Research · doi:10.1177/1178646918776658 · Cited by 200 · see citing works
Absence of SARM1 Rescues Development and Survival of NMNAT2-Deficient Axons
Gilley, J., Orsomando, G., Nascimento-Ferreira, I., & Coleman, M. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.02.060 · Cited by 196 · see citing works
“The GFP-NMN deamidase expression vector (pEGFP-C1-based) has been described previously (Di Stefano et al., 2014).”
MethodSelf-citationDeletion of Sarm1 gene is neuroprotective in two models of peripheral neuropathy
Turkiew, E., Falconer, D., Reed, N., & Höke, A. (2017) · Journal of the Peripheral Nervous System · doi:10.1111/jns.12219 · Cited by 182 · see citing works
“…what had been described in the literature with traumatic axon degeneration (Osterloh et al., 2012) and models of vincristine-induced neurotoxicity (Geisler et al., 2016; Gerdts et al., 2013), these results suggest an important role for Sarm1 in axon degeneration induced by both toxic and…”
BackgroundZhao, Z. Y., Xie, X. J., Li, W. H., Liu, J., Chen, Z., Zhang, B., Li, T., Li, S. L., Lu, J. G., Zhang, L., et al. (2019) · iScience · doi:10.1016/j.isci.2019.05.001 · Cited by 179 · see citing works
“After injury, nicotinamide mononucleotide (NMN) accumulates (Di Stefano et al., 2015) and intracellular Ca2+ rises in the injured axons (Loreto et al., 2015), followed by NAD depletion and axonal fragmentation.”
BackgroundHong, W., Mo, F., Zhang, Z., Huang, M., & Wei, X. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00246 · Cited by 179 · see citing works
Geisler, S., Doan, R. A., Cheng, G., Cetinkaya‐Fisgin, A., Huang, S. X., Höke, A., Milbrandt, J., & DiAntonio, A. (2019) · JCI Insight · doi:10.1172/jci.insight.129920 · Cited by 146 · see citing works
Structural basis of SARM1 activation, substrate recognition, and inhibition by small molecules
Shi, Y. Y., Kerry, P. S., Nanson, J. D., Bosanac, T., Sasaki, Y., Krauss, R., Saikot, F. K., Adams, S. E., Mosaiab, T., Masic, V., et al. (2022) · Molecular Cell · doi:10.1016/j.molcel.2022.03.007 · Cited by 146 · see citing works
Shared TIR enzymatic functions regulate cell death and immunity across the tree of life
Essuman, K., Milbrandt, J., Dangl, J. L., & Nishimura, M. T. (2022) · Science · doi:10.1126/science.abo0001 · Cited by 139 · see citing works
Figley, M. D., & DiAntonio, A. (2020) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2020.02.012 · Cited by 145 · see citing works
Loreto, A., Hill, C. S., Hewitt, V. L., Orsomando, G., Angeletti, C., Gilley, J., Lucci, C., Sanchez-Martinez, A., Whitworth, A. J., Conforti, L., et al. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104678 · Cited by 131 · see citing works
Self-citationCambronne, X. A., & Kraus, W. L. (2020) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2020.05.010 · Cited by 137 · see citing works
Structural and Mechanistic Regulation of the Pro-degenerative NAD Hydrolase SARM1
Bratkowski, M. A., Xie, T., Thayer, D. A., Lad, S., Mathur, P., Yang, Y.-S., Danko, G., Burdett, T. C., Danao, J., Cantor, A. J., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107999 · Cited by 132 · see citing works
Loreto, A., Stefano, M. D., Gering, M., & Conforti, L. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.11.032 · Cited by 128 · see citing works
“Ca2+ Imaging and Quantification in Zebrafish Larvae Zebrafish larvae were grown, transfected, axotomised, and imaged as described (Di Stefano et al., 2014) and as detailed in the Supplemental Experimental Procedures.”
BackgroundMethodResultInfluentialSelf-citationNMNAT2:HSP90 Complex Mediates Proteostasis in Proteinopathies
Ali, Y., Allen, H. M., Yu, L., Li‐Kroeger, D., Bakhshizadehmahmoudi, D., Hatcher, A., Aubin, C., Xu, J., Bjorklund, N. L., Taglialatela, G., et al. (2016) · PLoS Biology · doi:10.1371/journal.pbio.1002472 · Cited by 128 · see citing works
Krauss, R., Bosanac, T., Devraj, R. V., Engber, T. M., & Hughes, R. O. (2020) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2020.01.006 · Cited by 125 · see citing works
Structural basis for SARM1 inhibition and activation under energetic stress
Sporny, M., Guez-Haddad, J., Khazma, T., Yaron, A., Dessau, M. A., Shkolnisky, Y., Mim, C., Isupov, M. N., Zalk, R., Hons, M., et al. (2020) · eLife · doi:10.7554/elife.62021 · Cited by 125 · see citing works
The Safety and Antiaging Effects of Nicotinamide Mononucleotide in Human Clinical Trials: an Update
Song, Q., Zhou, X., Xu, K., Liu, S., Zhu, X., & Yang, J. J. (2023) · Advances in Nutrition · doi:10.1016/j.advnut.2023.08.008 · Cited by 122 · see citing works
“For instance, Di Stefano et al. [193,194] reported a prodegenerative effect on axons after NMN supplementation in a chemotherapy-induced peripheral neuropathy mouse model.”
BackgroundPark, J. H., Long, A. N., Owens, K., & Kristián, T. (2016) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.07.018 · Cited by 121 · see citing works
Liu, H.-W., Smith, C. B., Schmidt, M. S., Cambronne, X. A., Cohen, M. S., Migaud, M. E., Brenner, C., & Goodman, R. H. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1809392115 · Cited by 105 · see citing works
Mitochondrial division inhibitor (mdivi-1) decreases oxidative metabolism in cancer
Dai, W., Wang, G., Chwa, J. S., Oh, M. E., Abeywardana, T., Yang, Y., Wang, Q. A., & Jiang, L. (2020) · British Journal of Cancer · doi:10.1038/s41416-020-0778-x · Cited by 104 · see citing works
Glaucoma as a Metabolic Optic Neuropathy: Making the Case for Nicotinamide Treatment in Glaucoma
Williams, P. A., Harder, J. M., & John, S. W. M. (2017) · Journal of Glaucoma · doi:10.1097/ijg.0000000000000767 · Cited by 102 · see citing works
Stefano, M. D., Loreto, A., Orsomando, G., Mori, V., Zamporlini, F., Hulse, R. P., Webster, J., Donaldson, L. F., Gering, M., Raffaelli, N., et al. (2017) · Current Biology · doi:10.1016/j.cub.2017.01.070 · Cited by 95 · see citing works
“NMNDeamidase Expression ConfersMorphological and Functional Preservation of Transected Axons We previously reported that NMN deamidase expression confers protection against injury-induced axon degeneration in primary neuronal cultures similar to WLD [11, 13].”
BackgroundResultInfluentialSelf-citationAngeletti, C., Amici, A., Gilley, J., Loreto, A., Trapanotto, A. G., Antoniou, C., Merlini, E., Coleman, M. P., & Orsomando, G. (2022) · iScience · doi:10.1016/j.isci.2022.103812 · Cited by 95 · see citing works
Self-citationLiao, B., Zhao, Y., Wang, D., Zhang, X., Xuan-ming, H., & Hu, M. (2021) · Journal of the International Society of Sports Nutrition · doi:10.1186/s12970-021-00442-4 · Cited by 96 · see citing works
“Pharmacological dose of NA and nicotinamide (NAM) may result in painful flushing, liver damage and NAM exhibit sirtuin-inhibiting effects [44, 45], whereas NMN and NR exhibit better pharmacokinetic and pharmacological properties [17, 46–48].”
BackgroundNAD+ therapy in age-related degenerative disorders: A benefit/risk analysis
Braidy, N., & Liu, Y. (2020) · Experimental Gerontology · doi:10.1016/j.exger.2020.110831 · Cited by 96 · see citing works
Axon injury signaling and compartmentalized injury response in glaucoma
Syc‐Mazurek, S. B., & Libby, R. T. (2019) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2019.07.002 · Cited by 91 · see citing works
Nicotinamide ribose ameliorates cognitive impairment of aged and Alzheimer’s disease model mice
Xie, X. M., Gao, Y., Zeng, M., Wang, Y., Wei, T.-F., Lu, Y., & Zhang, W. (2018) · Metabolic Brain Disease · doi:10.1007/s11011-018-0346-8 · Cited by 88 · see citing works
Vaur, P., Brugg, B., Mericskay, M., Li, Z., Schmidt, M. S., Vivien, D., Orset, C., Jacotot, E. D., Brenner, C., & Duplus, E. (2017) · The FASEB Journal · doi:10.1096/fj.201700221rr · Cited by 86 · see citing works
“In PNS-derived neurons injured by axotomy, the cytoplasmicNADbiosynthetic enzymeNmnat2 is reportedly unstable, leading to axonal NMN accumulation, which has been described as deleterious and accelerating AxD (27).”
BackgroundGilley, J., Jackson, O., Pipis, M., Estiar, M. A., Al‐Chalabi, A., Danzi, M. C., van Eijk, K. R., Goutman, S. A., Harms, M. B., Houlden, H., et al. (2021) · eLife · doi:10.7554/elife.70905 · Cited by 84 · see citing works
Self-citationAxon degeneration: context defines distinct pathways
Geden, M. J., & Deshmukh, M. (2016) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2016.05.002 · Cited by 84 · see citing works
Autophagy in axonal degeneration in glaucomatous optic neuropathy
Munemasa, Y., & Kitaoka, Y. (2015) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2015.03.002 · Cited by 81 · see citing works
Selective inhibitors of SARM1 targeting an allosteric cysteine in the autoregulatory ARM domain
Feldman, H. C., Merlini, E., Guijas, C., DeMeester, K. E., Njomen, E., Kozina, E. M., Yokoyama, M., Vinogradova, E. V., Reardon, H. T., Melillo, B. N., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2208457119 · Cited by 79 · see citing works
Self-citationSARM1 depletion rescues NMNAT1-dependent photoreceptor cell death and retinal degeneration
Sasaki, Y., Kakita, H., Kubota, S., Sène, A., Lee, T. J., Ban, N., Dong, Z., Lin, J. B., Boye, S. L., DiAntonio, A., et al. (2020) · eLife · doi:10.7554/elife.62027 · Cited by 77 · see citing works
Nicotinamide Adenine Dinucleotide Metabolism and Neurodegeneration
Pehar, M., Harlan, B. A., Killoy, K. M., & Vargas, M. R. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7145 · Cited by 77 · see citing works
Self-citationRole of SARM1 and DR6 in retinal ganglion cell axonal and somal degeneration following axonal injury
Fernandes, K. A., Mitchell, K. L., Patel, A. K., Marola, O. J., Shrager, P. G., Zack, D. J., Libby, R. T., & Welsbie, D. S. (2018) · Experimental Eye Research · doi:10.1016/j.exer.2018.03.007 · Cited by 77 · see citing works
Emergence of SARM1 as a Potential Therapeutic Target for Wallerian-type Diseases
Loring, H. S., & Thompson, P. R. (2019) · Cell chemical biology · doi:10.1016/j.chembiol.2019.11.002 · Cited by 72 · see citing works
Axon death signalling in Wallerian degeneration among species and in disease
Rosell, A. L., & Neukomm, L. J. (2019) · Open Biology · doi:10.1098/rsob.190118 · Cited by 74 · see citing works
Ruggieri, S., Orsomando, G., Sorci, L., & Raffaelli, N. (2015) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2015.02.021 · Cited by 71 · see citing works
“The latter results however are in contrast with those from experiments performed on the same cultured cells and in vivo, showing that NamPRT inhibition protects from degeneration, despite lowering NAD [92].”
ResultSelf-citationKeeping the balance in NAD metabolism
Strømland, Ø., Niere, M., Nikiforov, A. A., VanLinden, M. R., Heiland, I., & Ziegler, M. (2019) · Biochemical Society Transactions · doi:10.1042/bst20180417 · Cited by 72 · see citing works
β-nicotinamide mononucleotide (NMN) production in Escherichia coli
Marinescu, G. C., Popescu, R. G., Stoian, G., & Dinischiotu, A. (2018) · Scientific Reports · doi:10.1038/s41598-018-30792-0 · Cited by 70 · see citing works
Neurotoxin-mediated potent activation of the axon degeneration regulator SARM1
Loreto, A., Angeletti, C., Gu, W., Osborne, A., Nieuwenhuis, B., Gilley, J., Arthur‐Farraj, P., Merlini, E., Amici, A., Luo, Z., et al. (2021) · eLife · doi:10.7554/elife.72823 · Cited by 70 · see citing works
Self-citationHomozygous NMNAT2 mutation in sisters with polyneuropathy and erythromelalgia
Huppke, P., Wegener, E., Gilley, J., Angeletti, C. A., Kurth, I., Drenth, J. P. H., Stadelmann, C., Barrantes‐Freer, A., Brück, W., Thiele, H., et al. (2019) · Experimental Neurology · doi:10.1016/j.expneurol.2019.112958 · Cited by 67 · see citing works
Self-citationArthur‐Farraj, P., & Coleman, M. P. (2021) · Neurotherapeutics · doi:10.1007/s13311-021-01125-3 · Cited by 62 · see citing works
“Loss of NMNAT2 from injured axons leads to accumulation of its substrate, NMN, which was found to promote axon degeneration [52].”
Self-citationWillemen, H. L. D. M., Ribeiro, P. S. S., Broeks, M. H., Meijer, N. W. F., Versteeg, S., Tiggeler, A., de Boer, T. P., Małecki, J., Falnes, P. Ø., Jans, J. J. M., et al. (2023) · Cell Reports Medicine · doi:10.1016/j.xcrm.2023.101265 · Cited by 64 · see citing works
Implications of NAD metabolism in pathophysiology and therapeutics for neurodegenerative diseases
Hikosaka, K., Yaku, K., Okabe, K., & Nakagawa, T. (2021) · Nutritional Neuroscience · doi:10.1080/1028415x.2019.1637504 · Cited by 62 · see citing works
Structural Evolution of TIR-Domain Signalosomes
Nimma, S., Gu, W., Maruta, N., Li, Y., Pan, M., Saikot, F. K., Lim, B. Y. J., McGuinness, H. Y., Zaoti, Z. F., Li, S., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.784484 · Cited by 63 · see citing works
SARM: From immune regulator to cell executioner
Carty, M., & Bowie, A. (2019) · Biochemical Pharmacology · doi:10.1016/j.bcp.2019.01.005 · Cited by 59 · see citing works
“Interestingly expression of E Coli NMN deamidase, which was also shown to protect damaged axons [84], also blocked SARM dependent depletion of NAD+ [83].”
BackgroundInfluentialMitochondrial dysfunction as a trigger of programmed axon death
Merlini, E., Coleman, M. P., & Loreto, A. (2021) · Trends in Neurosciences · doi:10.1016/j.tins.2021.10.014 · Cited by 57 · see citing works
Self-citationThe Drama of Wallerian Degeneration: The Cast, Crew, and Script
Zhang, K., Jiang, M., & Fang, Y. (2021) · Annual Review of Genetics · doi:10.1146/annurev-genet-071819-103917 · Cited by 57 · see citing works
Feng, J., Yan, P.-F., Zhao, H., Zhang, F., Zhao, W., & Feng, M. (2016) · BioMed Research International · doi:10.1155/2016/1450843 · Cited by 55 · see citing works
Maynard, M. E., Redell, J. B., Zhao, J., Hood, K. N., Vita, S. M., Kobori, N., & Dash, P. K. (2020) · Experimental Neurology · doi:10.1016/j.expneurol.2020.113207 · Cited by 55 · see citing works
“However, a recent study has reported that NMN can promote axon degeneration (Stefano et al., 2014).”
BackgroundEvaluation of the Aging Effect on Peripheral Nerve Regeneration: A Systematic Review
Maita, K. C., Garcia, J. P., Ávila, F. R., Torres‐Guzman, R. A., Ho, O. A., Chini, C. C. S., Chini, E. N., & Forte, A. J. (2023) · Journal of Surgical Research · doi:10.1016/j.jss.2023.03.017 · Cited by 49 · see citing works
Pharmacology and Potential Implications of Nicotinamide Adenine Dinucleotide Precursors
She, J., Sheng, R., & Qin, Z. (2021) · Aging and Disease · doi:10.14336/ad.2021.0523 · Cited by 49 · see citing works
Chen, X., Bahramimehr, F., Shahhamzehei, N., Fu, H., Lin, S., Wang, H., Li, C., Efferth, T., & Hong, C. (2024) · Phytomedicine · doi:10.1016/j.phymed.2024.155665 · Cited by 50 · see citing works
Local axonal protection by WldS as revealed by conditional regulation of protein stability
Wang, J. T., Medress, Z., Vargas, M. E., & Barres, B. (2015) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1508337112 · Cited by 43 · see citing works
“That the addition of only NAD+ or its immediate precursor NMN, but not other NAD metabolites, resulted in axonal protection demonstrates that NAD+ is specifically capable of delaying the course of axonal degeneration after injury.”
BackgroundInfluentialSelf-citationSARM1 signaling mechanisms in the injured nervous system
Sambashivan, S., & Freeman, M. R. (2021) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2021.05.004 · Cited by 46 · see citing works
A Novel NAD Signaling Mechanism in Axon Degeneration and its Relationship to Innate Immunity
Hopkins, E. L., Gu, W., Kobe, B., & Coleman, M. P. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.703532 · Cited by 46 · see citing works
Self-citationNeurotoxins subvert the allosteric activation mechanism of SARM1 to induce neuronal loss
Wu, T., Zhu, J., Strickland, A. M., Ko, K. W., Sasaki, Y., Dingwall, C. B., Yamada, Y., Figley, M. D., Mao, X. R., Neiner, A., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109872 · Cited by 45 · see citing works
Injury-Induced Inhibition of Bystander Neurons Requires dSarm and Signaling from Glia
Hsu, J.-M., Kang, Y., Corty, M. M., Mathieson, D., Peters, O. M., & Freeman, M. R. (2020) · Neuron · doi:10.1016/j.neuron.2020.11.012 · Cited by 44 · see citing works
NMNAT2 is a druggable target to drive neuronal NAD production
Tribble, J. R., Jöe, M., Varricchio, C., Otmani, A., Canovai, A., Habchi, B., Daskalakis, E., Chaleckis, R., Loreto, A., Gilley, J., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-50354-5 · Cited by 43 · see citing works
“Similarly, Fang et al. 9 demonstrated that gene therapy delivery of Nmnat2 Δ ex6, a more stable cytosolic form of NMNAT2, is also neuroprotective.”
Self-citationWallerian degeneration as a therapeutic target in traumatic brain injury
Koliatsos, V. E., & Alexandris, A. S. (2019) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000763 · Cited by 43 · see citing works
“Delayed treatment of in-vitro transected axons with the NAMPT inhibitor FK866 up to 4 h postinjury also suppresses Wallerian degeneration [99].”
BackgroundMechanisms and repair strategies for white matter degeneration in CNS injury and diseases
Shahsavani, N., Kataria, H., & Karimi‐Abdolrezaee, S. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2021.166117 · Cited by 42 · see citing works
Multi-targeted Effect of Nicotinamide Mononucleotide on Brain Bioenergetic Metabolism
Klimova, N., & Kristián, T. (2019) · Neurochemical Research · doi:10.1007/s11064-019-02729-0 · Cited by 42 · see citing works
Han, X., Bao, X., Lou, Q., Xie, X. M., Zhang, M., Zhou, S., Guo, H., Jiang, G., & Shi, Q. (2019) · PeerJ · doi:10.7717/peerj.7568 · Cited by 42 · see citing works
Sirtuins are not conserved longevity genes
Brenner, C. (2022) · Life Metabolism · doi:10.1093/lifemeta/loac025 · Cited by 42 · see citing works
“…metabolomics 113 has revealed that the NAD system is functionally disturbed by conditions of metabolic stress including fatty liver 114 , peripheral 115 and central 116 neurodegeneration, noise-induced hearing loss 117 , DNA damage 118 , heart failure 119 , postpartum 120 , activation of specific…”
BackgroundYaku, K., Palikhe, S., Iqbal, T., Hayat, F., Watanabe, Y., Fujisaka, S., Izumi, H., Yoshida, T., Karim, M., Uchida, H., et al. (2025) · Science Advances · doi:10.1126/sciadv.adr1538 · Cited by 40 · see citing works
NAD+ Precursors: A Questionable Redundancy
Cantó, C. (2022) · Metabolites · doi:10.3390/metabo12070630 · Cited by 41 · see citing works
Balancing NAD+ deficits with nicotinamide riboside: therapeutic possibilities and limitations
Cercillieux, A., Ciarlo, E., & Cantó, C. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04499-5 · Cited by 41 · see citing works
Vincristine- and bortezomib-induced neuropathies – from bedside to bench and back
Geisler, S. (2020) · Experimental Neurology · doi:10.1016/j.expneurol.2020.113519 · Cited by 40 · see citing works
NAD salvage pathway machinery expression in normal and glaucomatous retina and optic nerve
Tribble, J. R., Hagström, A., Jusseaume, K., Lardner, E., Wong, R. C. B., Stålhammar, G., & Williams, P. A. (2023) · Acta Neuropathologica Communications · doi:10.1186/s40478-023-01513-0 · Cited by 39 · see citing works
Nicotinic acid mononucleotide is an allosteric SARM1 inhibitor promoting axonal protection
Sasaki, Y., Zhu, J., Shi, Y. Y., Gu, W., Kobe, B., Ve, T., DiAntonio, A., & Milbrandt, J. (2021) · Experimental Neurology · doi:10.1016/j.expneurol.2021.113842 · Cited by 39 · see citing works
Metabolic aspects of neuronal degeneration: From a NAD+ point of view
Sasaki, Y. (2018) · Neuroscience Research · doi:10.1016/j.neures.2018.07.001 · Cited by 37 · see citing works
Mechanisms of injury-induced axon degeneration
Ding, C., & Hammarlund, M. (2019) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2019.03.006 · Cited by 36 · see citing works
Liang, Y., Li, M., Tang, Y., Yang, J., Wang, J., Zhu, Y., Liang, H., Lin, Q., Cheng, Y., Yang, X., et al. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115431 · Cited by 35 · see citing works
French, S. W. (2016) · Experimental and Molecular Pathology · doi:10.1016/j.yexmp.2016.02.004 · Cited by 34 · see citing works
Mitochondria and Caspases Tune Nmnat-Mediated Stabilization to Promote Axon Regeneration
Chen, L., Nye, D. M. R., Stone, M. C., Weiner, A. T., Gheres, K. W., Xiong, X., Collins, C. A., & Rolls, M. M. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1006503 · Cited by 34 · see citing works
Fortunato, C., Mazzola, F., & Raffaelli, N. (2021) · IUBMB Life · doi:10.1002/iub.2584 · Cited by 34 · see citing works
Brief Electrical Stimulation Promotes Recovery after Surgical Repair of Injured Peripheral Nerves
Gordon, T. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25010665 · Cited by 32 · see citing works
The NAD+ precursor NMN activates dSarm to trigger axon degeneration in Drosophila
Rosell, A. L., Paglione, M., Gilley, J., Kocia, M., Perillo, G., Gasparrini, M., Cialabrini, L., Raffaelli, N., Angeletti, C., Orsomando, G., et al. (2022) · eLife · doi:10.7554/elife.80245 · Cited by 29 · see citing works
Self-citationNMN: The NAD precursor at the intersection between axon degeneration and anti-ageing therapies
Loreto, A., Antoniou, C., Merlini, E., Gilley, J., & Coleman, M. P. (2023) · Neuroscience Research · doi:10.1016/j.neures.2023.01.004 · Cited by 30 · see citing works
Self-citationRoles of palmitoylation in axon growth, degeneration and regeneration
Holland, S. M., & Thomas, G. M. (2017) · Journal of Neuroscience Research · doi:10.1002/jnr.24003 · Cited by 29 · see citing works
“Readers interested in this issue, and in ‘downstream’ mechanisms that trigger axon degeneration following NMNAT2 loss are directed to this and other recent reports (Di Stefano et al., 2015; Gerdts et al., 2015; Gerdts et al., 2016; Summers et al., 2016; Yang et al., 2015).”
Background
- Authors
- Di Stefano, M., Nascimento-Ferreira, I., Orsomando, G., Mori, V, Gilley, J., Brown, R., Janeckova, L., Vargas, M. E., Worrell, L. A., Loreto, A., Tickle, J., Patrick, J., Webster, J. R. M., Marangoni, M., Carpi, F. M., Pucciarelli, S., Rossi, F., Meng, W., Sagasti, A., Ribchester, R. R., Magni, G., Coleman, M. P., & Conforti, L.
- Affiliations
- Babraham Institute (GB)
- Marche Polytechnic University (IT)
- University of Edinburgh (GB)
- University of California, Los Angeles (US)
- University of Nottingham (GB)
- Università di Camerino (IT)
- Corresponding author
- Coleman, M P
- Conforti, L
- ORCID
- Venue
- Cell Death & Differentiation
- Published
- 2014-10-17
- Volume
- 22
- Issue
- 5
- Pages
- 731-742
- ISSN
- 1350-9047 (ISSN-L)
- 1476-5403
- PMC
- PMC4392071
- OpenAlex
- W2128749718
- Cited by
- 246
- References
- 64
- Citations by year
- 2026: 10 · 2025: 18 · 2024: 22 · 2023: 28 · 2022: 34 · 2021: 30 · 2020: 31 · 2019: 19 · 2018: 14 · 2017: 13 · 2016: 13 · 2015: 10 · 2014: 3
- FWCI
- 6.09
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell Death and Differentiation (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Unicam Scientific Publications (University of Camerino) (submittedVersion, other-oa)
- Apollo (University of Cambridge) (submittedVersion, cc-by-nc-nd)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
- Apollo
- Funders
- Directorate for Biological Sciences
- Biotechnology and Biological Sciences Research Council (BBS/E/B/000C0417)
- Faculty of Medicine and Health, University of Sydney
- National Institute of Mental Health
- National Institute of Dental and Craniofacial Research (1R01DE019487)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- nicotinamide mononucleotide, NAD biosynthesis, NMNAT2, axonal degeneration, nerve injury, visfatin, FK866, axon survival, axonopathy, cancer chemotherapy
- MeSH terms
- Amidohydrolases, Animals, Axons, Bacterial Proteins, Nerve Degeneration, Nicotinamide Mononucleotide, Nicotinamide-Nucleotide Adenylyltransferase, Mice, Peripheral Nerve Injuries
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
