Nicotinamide mononucleotide adenylyltransferase expression in mitochondrial matrix delays Wallerian degeneration
Open accessAbstract
Studies of naturally occurring mutant mice,wld s, showing delayed Wallerian degeneration phenotype, suggest that axonal degeneration is an active process. We previously showed that increased nicotinamide adenine dinucleotide (NAD)-synthesizing activity by overexpression of nicotinamide mononucleotide adenylyltransferase (NMNAT) is the essential component of the Wld s protein, the expression of which is responsible for the delayed Wallerian degeneration phenotype in wld smice. Indeed, NMNAT overexpression in cultured neurons provides robust protection to neurites, as well. To examine the effect of NMNAT overexpression in vivo and to analyze the mechanism that causes axonal protection, we generated transgenic mice (Tg) overexpressing NMNAT1 (nuclear isoform), NMNAT3 (mitochondrial isoform), or the Wld s protein bearing a W258A mutation, which disrupts NAD-synthesizing activity of the Wld s protein. Wallerian degeneration delay in NMNAT3-Tg was similar to that in wld smice, whereas axonal protection in NMNAT1-Tg or Wld s(W258A)-Tg was not detectable. Detailed analysis of subcellular localization of the overexpressed proteins revealed that the axonal protection phenotype was correlated with localization of NMNAT enzymatic activity to mitochondrial matrix. Furthermore, we found that isolated mitochondria from mice showing axonal protection expressed unchanged levels of respiratory chain components, but were capable of increased ATP production. These results suggest that axonal protection by NMNAT expression in neurons is provided by modifying mitochondrial function. Alteration of mitochondrial function may constitute a novel tool for axonal protection, as well as a possible treatment of diseases involving axonopathy.
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In mammals, over-expressing NMNATs significantly delays Wallerian degeneration of peripheral nerves.
“In mammals, over-expressing NMNATs significantly delays Wallerian degeneration of peripheral nerves (28)(29)(30)(31)(32)(33).”
From CREB-activity and nmnat2 transcription are down-regulated prior to neurodegeneration, while NMNAT2 over-expression is neuroprotective, in a mouse model of human tauopathy (2012) · cites this paper as [33]
In the Results section on transgenic overexpression (Figs. 2–3), NMNAT3-overexpressing mice showed a significant delay in degeneration of transected sciatic nerves. The claim generalizes this effect to NMNATs, but the same section reports no detectable delay in NMNAT1-overexpressing mice. (LLM, conf=0.88)
Experimental — accuracy not yet measuredNMNAT3-transgenic mice show delayed Wallerian degeneration similar to WldS mice.
“NMNAT3-transgenic mice show delayed Wallerian degeneration similar to Wld S mice (33).”
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InfluentialWallerian Degeneration, Wld<sup>S</sup>, and Nmnat
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“32 Further, it was reported that transgenic mice overexpressing NMNAT3 had a significant number of preserved axons in injured sciatic nerves, whereas wild-type mice had mostly degraded axons in injured nerves.(33) Thus, increased Nmnat3 levels both in vitro and in vivo when using transgenic mice and local overexpressi…”
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“NMNAT3-transgenic mice show delayed Wallerian degeneration similar to Wld mice (33).”
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“In support of this hypothesis, overexpression of Wld s, or its component Nmnat, blocks degeneration in response to many distinct stimuli (Mack et al., 2001; Ferri et al., 2003; Araki et al., 2004; Sasaki et al., 2006, 2009a,b; Yahata et al., 2009).”
BackgroundNMNATs, evolutionarily conserved neuronal maintenance factors
Ali, Y. O., Li-Kroeger, D., Bellen, H. J., Zhai, R. G., & Lu, H.-C. (2013) · Trends in Neurosciences · doi:10.1016/j.tins.2013.07.002 · Cited by 91 · see citing works
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“In vivo, NMNAT1 overexpression was not sufficient for axon protection, but NMNAT3 targeted to the mitochondrial matrix protected sciatic nerves after axotomy (Yahata et al., 2009).”
BackgroundInfluentialWldS and PGC-1α Regulate Mitochondrial Transport and Oxidation State after Axonal Injury
O’Donnell, K. C., Vargas, M. E., & Sagasti, A. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.1331-13.2013 · Cited by 100 · see citing works
“For example, mitochondria isolated from WldS-expressing axons exhibit increased ATP production (Yahata et al., 2009) and calcium buffering (Avery et al., 2012), and a recent study found a correlation between mitochondrial transport and axon protection by WldS (Avery et al., 2012).”
BackgroundMitochondrial Behavior in Axon Degeneration and Regeneration
Wang, B., Huang, M., Shang, D., Yan, X., Zhao, B., & Zhang, X. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.650038 · Cited by 90 · see citing works
“, 2015), the activity of which is greatly inhibited by defects in healthy mitochondria, decreases in mitochondrial transport, and ROS accumulation during axon degeneration (Yahata et al., 2009; Avery et al., 2012; Fang et al., 2012; O’Donnell et al., 2013).”
BackgroundBarrette, B., Calvo, E. L., Vallières, N., & Lacroix, S. (2010) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2010.07.249 · Cited by 95 · see citing works
“…a level of axon protection that is similar (or superior) to that seen in WldS mice (Avery et al., 2009; Beirowski et al., 2009; Sasaki et al., 2009; Yahata et al., 2009), suggests that the function of the N16-VPC/p97 complex may be to relocalize NMNAT1 from the nuclear to the cyto- solic and…”
Nmnat2 delays axon degeneration in superior cervical ganglia dependent on its NAD synthesis activity
Yan, T., Feng, Y., Zheng, J., Ge, X., Zhang, Y., Wu, D., Zhao, J., & Zhai, Q. (2010) · Neurochemistry International · doi:10.1016/j.neuint.2009.09.007 · Cited by 92 · see citing works
Axonal Degeneration in AD: The Contribution of Aβ and Tau
Salvadores, N., Gerónimo‐Olvera, C., & Court, F. A. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.581767 · Cited by 97 · 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, NR is protective reportedly because Nmrk2 is transcriptionally up-regulated by the injury (7).”
BackgroundInfluentialKilinc, D., Peyrin, J., Soubeyre, V., Magnifico, S., Saïas, L., Viovy, J., & Brugg, B. (2010) · Neurotoxicity Research · doi:10.1007/s12640-010-9152-8 · Cited by 82 · see citing works
“2004) but not in vivo axotomy (Conforti et al. 2007; Yahata et al. 2009).”
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
Hikosaka, K., Ikutani, M., Shito, M., Kazuma, K., Gulshan, M., Nagai, Y., Takatsu, K., Konno, K., Tobe, K., Kanno, H., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.554378 · Cited by 81 · see citing works
“Nmnat3 overexpression confers robust protection against axon injury in vitro and in vivo as well as WldS chimeric protein (27, 28).”
BackgroundA 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 · see citing works
“…includes the mitochondrial permeability transition pore (Forte et al., 2007; Barrientos et al., 2011) and can be blocked by axonal expression of NMNAT isoforms (Araki et al., 2004; Conforti et al., 2009; Sasaki et al., 2009a; Yahata et al., 2009; Babetto et al., 2010; Sasaki and Milbrandt, 2010).”
BackgroundSignaling mechanisms regulating Wallerian degeneration
Freeman, M. R. (2014) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2014.05.001 · 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
Chandrasekaran, K., Salimian, M., Konduru, S. R., Choi, J., Kumar, P., Long, A. N., Klimova, N., Ho, C.-Y., Kristián, T., & Russell, J. W. (2019) · Brain · doi:10.1093/brain/awz324 · Cited by 71 · see citing works
“Proteins that resynthesize NAD + via the salvage pathway such as NMNAT1–3, protect against axonal degeneration (Araki et al., 2004; Press and Milbrandt, 2008; Sasaki et al., 2009; Yahata et al., 2009; Babetto et al., 2010; Gilley and Coleman, 2010; Di Stefano et al., 2017).”
BackgroundZhu, Y., Zhang, L., Sasaki, Y., Milbrandt, J., & Gidday, J. M. (2012) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.12-10861 · Cited by 65 · see citing works
Tao, J., & Rolls, M. M. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.3826-10.2011 · Cited by 66 · see citing works
The Synaptic Proteome during Development and Plasticity of the Mouse Visual Cortex
Dahlhaus, M., Li, K. W., van der Schors, R. C., Saiepour, M. H., van Nierop, P., Heimel, J. A., Hermans, J. M., Loos, M., Smit, A. B., & Levelt, C. N. (2011) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m110.005413 · Cited by 60 · see citing works
“Several mechanisms have been implicated and include reduced mitochondrial activity (53), alterations in the ubiquitin/proteasome system (54), increased microtubule The Synaptic Proteome during Visual Plasticity”
BackgroundNMNAT: It’s an NAD+ synthase… It’s a chaperone… It’s a neuroprotector
Brazill, J. M., Li, C. V., Zhu, Y., & Zhai, R. G. (2017) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2017.03.014 · Cited by 73 · see citing works
Felici, R., Lapucci, A., Ramazzotti, M., & Chiarugi, A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0076938 · Cited by 63 · see citing works
“Later on, almost all the information collected on NMNAT3 localization and activity has been obtained by expression plasmids coding for tagged proteins [9,12,14].”
BackgroundNmnat exerts neuroprotective effects in dendrites and axons
Wen, Y., Parrish, J. Z., He, R., Zhai, R. G., & Kim, M. D. (2011) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2011.05.002 · Cited by 50 · see citing works
“…that the enzymatic activity of Nmnat is required for axonal protection (Avery et al., 2009; Conforti et al., 2009; Jia et al., 2007; Sasaki et al., 2009; Yahata et al., 2009; Yan et al., 2010), these studies have not directly addressed a neuroprotective role for Nmnat specifically in dendrites.”
BackgroundImplications 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
Sasaki, Y., & Milbrandt, J. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.c110.193904 · Cited by 66 · see citing works
Peters, O. M., Lewis, E. A., Osterloh, J. M., Weiss, A., Salameh, J. S., Metterville, J., Brown, R. H., & Freeman, M. R. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddy260 · Cited by 61 · see citing works
“Both proteins localize to mitochondria (33–35), with Sarm1 robustly protecting cultured neurons from the downstream reactive oxygen stress caused by mitochondria uncoupling (36).”
BackgroundAxon Degeneration and Regeneration: Insights from Drosophila Models of Nerve Injury
Fang, Y., & Bonini, N. M. (2012) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-101011-155836 · Cited by 57 · see citing works
Arthur‐Farraj, P., & Coleman, M. P. (2021) · Neurotherapeutics · doi:10.1007/s13311-021-01125-3 · Cited by 62 · see citing works
Ocampo, A., Liu, J., & Barrientos, A. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt016 · Cited by 47 · see citing works
NAD+: A key metabolic regulator with great therapeutic potential
Sultani, G., Samsudeen, A., Osborne, B., & Turner, N. A. (2017) · Journal of Neuroendocrinology · doi:10.1111/jne.12508 · Cited by 54 · see citing works
Owens, K., Park, J. H., Schuh, R. A., & Kristián, T. (2013) · Translational Stroke Research · doi:10.1007/s12975-013-0278-x · Cited by 53 · see citing works
Kuo, C.-C., Su, H., Chang, T.-L., Chiang, C.-Y., Sheu, M., Cheng, F., Chen, C., Sheehan, J. P., & Pan, H.-C. (2017) · Neurosurgery · doi:10.1093/neuros/nyw090 · Cited by 54 · see citing works
Concepts for regulation of axon integrity by enwrapping glia
Beirowski, B. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00256 · Cited by 44 · see citing works
“This cytoplasmic NAD+ dependent sirtuin has been recently implicated in cellautonomous axonal stability mechanisms, toxin-induced axon degeneration, and the pathways mediating the WldS phenotype (Suzuki and Koike, 2007a,b; Wishart et al., 2012).”
BackgroundInfluentialThe role of autophagy in axonal degeneration of the optic nerve
Koch, J. C., & Lingor, P. (2016) · Experimental Eye Research · doi:10.1016/j.exer.2015.08.016 · Cited by 46 · see citing works
NAD + acts on mitochondrial SirT3 to prevent axonal caspase activation and axonal degeneration
Magnifico, S., Saïas, L., Deleglise, B., Duplus, E., Kilinc, D., Miquel, M., Viovy, J., Brugg, B., & Peyrin, J. (2013) · The FASEB Journal · doi:10.1096/fj.13-229781 · Cited by 51 · see citing works
“Accordingly, a recent study showed that overexpression of NMNAT3, a NAD producing enzyme, in the mitochondrial matrix increased axonal resistance to axotomy, suggesting that NMNAT-dependent axonal protection involves modulation of mitochondrial function modulation (55).”
BackgroundMilde, S., Fox, A. N., Freeman, M. R., & Coleman, M. P. (2013) · Scientific Reports · doi:10.1038/srep02567 · Cited by 44 · see citing works
Gulshan, M., Yaku, K., Okabe, K., Mahmood, A., Sasaki, T., Yamamoto, M., Hikosaka, K., Usui, I., Kitamura, T., Tobe, K., et al. (2018) · Aging Cell · doi:10.1111/acel.12798 · Cited by 49 · see citing works
“Nmnat3 mice were generated as described previously (Yahata et al., 2009).”
MethodFeng, Y., Yan, T., Zheng, J. H., Ge, X., Mu, Y., Zhang, Y., Wu, D., Du, J., & Zhai, Q. (2010) · Journal of Neuroscience Research · doi:10.1002/jnr.22498 · Cited by 46 · see citing works
“Overexpression of Nmnat3 protects axons in mice and Drosophila as well (Avery et al., 2009; Yahata et al., 2009).”
BackgroundLocal 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
“Although the WldS protein is localized predominantly in the nucleus because of the endogenous nuclear localization of Nmnat1, trace amounts of WldS protein also have been identified in extranuclear compartments in the axoplasm and in axonal organelles including the mitochondria and phagosomes (10, 11), suggesting that…”
BackgroundThe Role of Axonopathy in Parkinson's Disease
O’Malley, K. L. (2010) · Experimental Neurobiology · doi:10.5607/en.2010.19.3.115 · Cited by 33 · see citing works
“…subcellular localization studies have found substantial amounts of Wld S within the mitochondrial matrix where it may en-118 hance ATP synthesis (Yahata et al., 2009), prevent free radical formation (Press and Milbrandt, 2009), or maintain mitochondrial membrane potential (Ike-gami and Koike,…”
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
Preserve and protect: maintaining axons within functional circuits
Pease-Raissi, S. E., & Segal, R. A. (2014) · Trends in Neurosciences · doi:10.1016/j.tins.2014.07.007 · Cited by 34 · see citing works
Mechanisms 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
Yaku, K., Okabe, K., Gulshan, M., Takatsu, K., Okamoto, H., & Nakagawa, T. (2019) · Scientific Reports · doi:10.1038/s41598-019-49547-6 · Cited by 38 · see citing works
Ali, Y., Bradley, G., & Lu, H. (2017) · Scientific Reports · doi:10.1038/srep43846 · Cited by 42 · see citing works
Vitamin B3, the nicotinamide adenine dinucleotides and aging
Xu, P., & Sauve, A. A. (2010) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2010.03.006 · Cited by 38 · see citing works
“Strikingly, NADand NAD precursors can also provide protection against axonal degeneration, suggesting that the effect of Nmnat1 is achieved through a function involving NAD synthesis (Sasaki et al., 2006, 2009; Press and Milbrandt, 2008; Wang and He, 2009; Yahata et al., 2009).”
BackgroundAxon degeneration: Mechanisms and implications of a distinct program from cell death
Yan, T., Feng, Y., & Zhai, Q. (2010) · Neurochemistry International · doi:10.1016/j.neuint.2010.01.013 · Cited by 36 · see citing works
“Studies suggested that overexpression of Wld and Nmnat1 might initiate their axonal protective function by increasing mitochondrial NAD or ATP production (Sasaki et al., 2009b; Yahata et al., 2009).”
InfluentialChandrasekaran, K., Najimi, N., Sagi, A. R., Yarlagadda, S., Salimian, M., Arvas, M. I., Hedayat, A. F., Kevas, Y., Kadakia, A., & Russell, J. W. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094887 · Cited by 37 · see citing works
Simultaneous Single-Sample Determination of NMNAT Isozyme Activities in Mouse Tissues
Orsomando, G., Cialabrini, L., Amici, A., Mazzola, F., Ruggieri, S., Conforti, L., Janečková, L., Coleman, M. P., & Magni, G. (2012) · PLoS ONE · doi:10.1371/journal.pone.0053271 · Cited by 36 · see citing works
“subcellular district [43,44], 3) incomplete recovery of a given”
BackgroundWldS but not Nmnat1 protects dopaminergic neurites from MPP+ neurotoxicity
Antenor‐Dorsey, J. A. V., & O’Malley, K. L. (2012) · Molecular Neurodegeneration · doi:10.1186/1750-1326-7-5 · Cited by 29 · see citing works
“In contrast, transgenic animals expressing nuclear Nmnat1 did not replicate the effects of Wld [42,43] whereas cytoplasmically [39] or axonally targeted Nmnat1 [34] were equally if not more effective.”
Hayes, L. R., Brotherton, T. E., & Glass, J. D. (2013) · Experimental Neurology · doi:10.1016/j.expneurol.2013.05.001 · Cited by 34 · see citing works
Poly(ADP-ribose) polymerase 1 is a novel target to promote axonal regeneration
Brochier, C., Jones, J. I., Willis, D. E., & Langley, B. C. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1509754112 · Cited by 39 · see citing works
“Underscoring the importance of axonal NAD+, many studies have shown that increasing axonal NAD+ via extra copies of the NAD+ recycling enzyme NMNAT (22, 54, 55) or providing exogenous NAD+ or its precursors can markedly delay axon degeneration after transection (22).”
BackgroundMaintaining 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
“There is compelling evidence indicating that NMNAT activity is required for WldS-mediated axon protection (Araki et al., 2004; Avery et al., 2009; Conforti et al., 2009; Yahata et al., 2009).”
BackgroundWilliams, A. C., Hill, L. J., & Ramsden, D. B. (2012) · Current Gerontology and Geriatrics Research · doi:10.1155/2012/302875 · Cited by 41 · see citing works
“Recent reviews on nicotinamide and NAD metabolism, evolution and function concentrate on its pivotal role in gene silencing, development and ageing, through recently appreciated NAD consumers, such as the sirtuins (SIRTs) [77–85], that evolved to work in large part as nutrientsensing regulators, and poly (ADP ribose)…”
BackgroundNicotinamide and neurocognitive function
Rennie, G. E., Chen, A. C., Dhillon, H. M., Vardy, J. L., & Damian, D. L. (2014) · Nutritional Neuroscience · doi:10.1179/1476830514y.0000000112 · Cited by 39 · see citing works
Axonal fusion: An alternative and efficient mechanism of nerve repair
Neumann, B., Linton, C., Giordano-Santini, R., & Hilliard, M. A. (2018) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2018.11.004 · Cited by 34 · see citing works
Coppedè, F., Bosco, P., Fuso, A., & Troen, A. M. (2012) · Current Gerontology and Geriatrics Research · doi:10.1155/2012/926082 · Cited by 4 · see citing works
The Molecular Interplay between Axon Degeneration and Regeneration
Girouard, M., Bueno, M., Julian, V., Drake, S., Byrne, A. B., & Fournier, A. E. (2018) · Developmental Neurobiology · doi:10.1002/dneu.22627 · Cited by 37 · see citing works
“Its activity partly depends on mitochondria and correlates with mitochondrial preservation, enhanced mitochondrial motility, and reactive oxygen species (ROS) stabilization (Yahata et al., 2009; Avery et al., 2012; Fang et al., 2012; O’Donnell et al., 2013).”
BackgroundWldS, Nmnats and axon degeneration-progress in the past two decades
Feng, Y., Yan, T., He, Z., & Zhai, Q. (2010) · Protein & Cell · doi:10.1007/s13238-010-0021-2 · Cited by 24 · see citing works
“Interestingly, Nmnat3 transgenic mice showed robust protection as Wld (Yahata et al., 2009), again supporting the protective effects of non-nuclear Nmnat and Wld proteins.”
BackgroundMethodInfluentialGlutamate signals through mGluR2 to control Schwann cell differentiation and proliferation
Saitoh, F., Wakatsuki, S., Tokunaga, S., Fujieda, H., & Araki, T. (2016) · Scientific Reports · doi:10.1038/srep29856 · Cited by 26
Self-citationMcGuinness, H. Y., Gu, W., Shi, Y. Y., Kobe, B., & Ve, T. (2023) · The Neuroscientist · doi:10.1177/10738584231162508 · Cited by 27 · see citing works
Axonal transport plays a crucial role in mediating the axon-protective effects of NmNAT
Fang, C., Decker, H., & Banker, G. A. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.04.013 · Cited by 18 · see citing works
“Moreover, mitochondria from Wld mice have an enhanced ability to generate ATP (Yahata et al., 2009) and expression of the Wld protein or various forms of NmNAT in cultured neurons reduces the decline in ATP levels that occur following axotomy (Wang et al.”
InfluentialMolecular chaperones protect against JNK- and Nmnat-regulated axon degeneration in Drosophila
Rallis, A., Lu, B., & Ng, J. (2012) · Journal of Cell Science · doi:10.1242/jcs.117259 · Cited by 19 · see citing works
Molecular mechanisms in the initiation phase of Wallerian degeneration
Chang, B., Quan, Q., Lu, S., Wang, Y., & Peng, J. (2016) · European Journal of Neuroscience · doi:10.1111/ejn.13250 · Cited by 21 · see citing works
“Although WLDs is predominantly located in nuclei, small quantities of WLDs are present in the axonal pool (Mack et al., 2001; Beirowski et al., 2005; Yahata et al., 2009).”
BackgroundAxon Degeneration: Where the Wlds Things Are
Wang, J. T., & Barres, B. A. (2012) · Current Biology · doi:10.1016/j.cub.2012.02.056 · Cited by 18 · see citing works
Pathobiochemistry of Aging and Neurodegeneration: Deregulation of NAD+ Metabolism in Brain Cells
Kolotyeva, N. A., Groshkov, A. A., Rozanova, N. A., Berdnikov, A. K., Novikova, S. V., Komleva, Y. K., Salmina, A. B., Illarioshkin, S. N., & Пирадов, М. А. (2024) · Biomolecules · doi:10.3390/biom14121556 · Cited by 22 · see citing works
“It was proposed that the subcellular distribution of NMNATs may dictate their organelle-specific functions [54–57].”
Moss, K. R., & Höke, A. (2019) · Brain Research · doi:10.1016/j.brainres.2019.146539 · Cited by 25 · see citing works
Intracellular signalling pathways in dopamine cell death and axonal degeneration
Burke, R. E. (2010) · Progress in brain research · doi:10.1016/s0079-6123(10)83005-5 · Cited by 22 · see citing works
“Interestingly, the full protection phenotype can be observed in experiments with NMNAT3, a mitochondrially targeted isoform (Avery et al., 2009; Sasaki et al., 2006; Yahata et al., 2009).”
Background
- Authors
- Yahata, N., Yuasa, S., & Araki, T.
- Affiliations
- National Center of Neurology and Psychiatry (JP)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2009-05-13
- Volume
- 29
- Issue
- 19
- Pages
- 6276-6284
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6665489
- OpenAlex
- W2037726118
- Cited by
- 154
- References
- 30
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 6 · 2021: 10 · 2020: 5 · 2019: 8 · 2018: 10 · 2017: 8 · 2016: 5 · 2015: 10 · 2014: 12 · 2013: 16 · 2012: 16
- FWCI
- 7.19
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Suzuken Memorial Foundation
- Kowa Company
- Kowa Life Science Foundation
- Astellas Pharma
- National Institute of Biomedical Innovation
- Astellas Foundation for Research on Metabolic Disorders
- Mishima Kaiun Memorial Foundation
- Japan Society for the Promotion of Science (19650089)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- nicotinamide mononucleotide adenylyltransferase, NMNAT3, NMNAT1, Wallerian degeneration, axonal degeneration, axonal protection, mitochondrial matrix, NAD biosynthesis, mitochondrial function, ATP production, transgenic mice, axonopathy
- MeSH terms
- Adenosine Triphosphate, Animals, Axons, Electron Transport, Mice, Transgenic, Mitochondria, Nerve Tissue Proteins, Neurons, Nicotinamide-Nucleotide Adenylyltransferase, Sciatic Nerve, Wallerian Degeneration, Mutation, Missense, Sciatic Neuropathy, Mice
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