CoChat
Sign Up
Cited by 324Sirtuins and Resveratrol in MedicineNerve injury and regenerationCell death mechanisms and regulation

SARM1 is a metabolic sensor activated by an increased NMN/NAD+ ratio to trigger axon degeneration

Open access
Figley, Matthew D., Gu, Weixi, Nanson, Jeffrey D., Shi, Yun, Sasaki, Yo, Cunnea, Katie, Malde, Alpeshkumar K., Jia, Xinying +17 more·2021·Neuron
DOI 10.1016/j.neuron.2021.02.009PMC PMC8174188
Open this paper in CoChat — free accountOpen PDF

Abstract

Axon degeneration is a central pathological feature of many neurodegenerative diseases. Sterile alpha and Toll/interleukin-1 receptor motif-containing 1 (SARM1) is a nicotinamide adenine dinucleotide (NAD+)-cleaving enzyme whose activation triggers axon destruction. Loss of the biosynthetic enzyme NMNAT2, which converts nicotinamide mononucleotide (NMN) to NAD+, activates SARM1 via an unknown mechanism. Using structural, biochemical, biophysical, and cellular assays, we demonstrate that SARM1 is activated by an increase in the ratio of NMN to NAD+ and show that both metabolites compete for binding to the auto-inhibitory N-terminal armadillo repeat (ARM) domain of SARM1. We report structures of the SARM1 ARM domain bound to NMN and of the homo-octameric SARM1 complex in the absence of ligands. We show that NMN influences the structure of SARM1 and demonstrate via mutagenesis that NMN binding is required for injury-induced SARM1 activation and axon destruction. Hence, SARM1 is a metabolic sensor responding to an increased NMN/NAD+ ratio by cleaving residual NAD+, thereby inducing feedforward metabolic catastrophe and axonal demise.

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.neuron.2021.02.009

Cites

4 of 4 references verified0 citation errors · 0 not checkable

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.

A few free checks a day · papers already verified open instantly · results are public

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?

  • Sarm1 acts as a metabolic sensor to monitor local NAD+ levels.

    “Along with NAD + synthase NMNAT2 at the upstream 54 , Sarm1 acts as a metabolic sensor to monitor local NAD + levels 12 .”

    From NAD+ hydrolase Sarm1 is a key driver of synapse degeneration and memory loss in Alzheimer’s disease (2025) · cites this paper as [12]

    The Discussion identifies SARM1 as a metabolic sensor, but specifies that it responds to the NMN/NAD+ ratio rather than NAD+ levels alone. The Results section on SARM1 activation in neurons likewise says the ratio predicts activation; the claim omits that qualification. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Sarm1 remains inactive in physiological conditions but becomes activated in pathological conditions.

    “For this reason, Sarm1 remains inactive in physiological conditions but becomes activated in pathological conditions 12,48 .”

    From NAD+ hydrolase Sarm1 is a key driver of synapse degeneration and memory loss in Alzheimer’s disease (2025) · cites this paper as [12]

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

Flagged first, then by citations

Research works printed but not linked: 97

  1. Afonine PV, Klaholz BP, Moriarty NW, Poon BK, Sobolev OV, Terwilliger TC, Adams PD, and Urzhumtsev A (2018). New tools for the analysis and validation of cryo-EM maps and atomic models. Acta Crystallogr. D Biol. Crystallogr 74, 814– 840. PMC6130467 30198894
  2. Araki T, Sasaki Y, and Milbrandt J (2004). Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration. Science 305, 1010– 1013. 15310905
  3. Bepler T, Morin A, Rapp M, Brasch J, Shapiro L, Noble AJ, and Berger B (2019). Positive-unlabeled convolutional neural networks for particle picking in cryo-electron micrographs. Nat. Methods 16, 1153– 1160. 31591578 PMC6858545
  4. Berendsen HJC, Postma JPM, van Gunsteren WF, and Hermans J (1981). Interaction Models for Water in Relation to Protein Hydration. In Intermolecular Forces: Proceedings of the Fourteenth Jerusalem Symposium on Quantum Chemistry and Biochemistry Held in Jerusalem, Israel, 4 13–16, 1981, Pullman B, ed. (Dordrecht: Springer Netherlands), pp. 331– 342.
  5. Bogan KL, and Brenner C (2008). Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition. Annu. Rev. Nutr 28, 115– 130. 18429699
  6. Bratkowski M, (2020). Structural and Mechanistic Regulation of the Pro-degenerative NAD Hydrolase SARM1. Cell Rep. 32, 107999. 32755591
  7. Case DA, (2005). The Amber biomolecular simulation programs. J. Comput. Chem 26, 1668– 1688. 16200636 PMC1989667
  8. Chen S, McMullan G, Faruqi AR, Murshudov GN, Short JM, Scheres SH, and Henderson R (2013). High-resolution noise substitution to measure overfitting and validate resolution in 3D structure determination by single particle electron cryomicroscopy. Ultramicroscopy 135, 24– 35. 23872039 PMC3834153
  9. Christen M, (2005). The GROMOS software for biomolecular simulation: GROMOS05. J. Comput. Chem 26, 1719– 1751. 16211540
  10. Chuang CF, and Bargmann CI (2005). A Toll-interleukin 1 repeat protein at the synapse specifies asymmetric odorant receptor expression via ASK1 MAPKKK signaling. Genes Dev. 19, 270– 281. 15625192 PMC545892
  11. Coleman MP, and Hoke A (2020). Programmed axon degeneration: from mouse to mechanism to medicine. Nat. Rev. Neurosci 21, 183– 196. 32152523 PMC8926152
  12. Di Stefano M, (2017). NMN Deamidase Delays Wallerian Degeneration and Rescues Axonal Defects Caused by NMNAT2 Deficiency In Vivo. Curr. Biol 27, 784– 794. 28262487
  13. Emsley P, and Cowtan KD (2004). Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr 60, 2126– 2132. 15572765
  14. Ernst P, Honegger A, van der Valk F, Ewald C, Mittl PRE, and Pluckthun A (2019). Rigid fusions of designed helical repeat binding proteins efficiently protect a binding surface from crystal contacts. Sci. Rep 9, 16162. 31700118 PMC6838082
  15. Essuman K, Summers DW, Sasaki Y, Mao X, DiAntonio A, and Milbrandt J (2017). The SARM1 Toll/interleukin-1 receptor domain possesses intrinsic NAD+ cleavage activity that promotes pathological axonal degeneration. Neuron 93, 1334– 1343. 28334607 PMC6284238
  16. Essuman K, Summers DW, Sasaki Y, Mao X, Yim AKY, DiAntonio A, and Milbrandt J (2018). TIR domain proteins are an ancient family of NAD(+)-consuming enzymes. Curr. Biol 28, 421– 430 e424. 29395922 PMC5802418
  17. Evans PR, and Murshudov GN (2013). How good are my data and what is the resolution? Acta Crystallogr. D Biol. Crystallogr 69, 1204– 1214. 23793146 PMC3689523
  18. Figley MD, and DiAntonio A (2020). The SARM1 axon degeneration pathway: control of the NAD(+) metabolome regulates axon survival in health and disease. Curr. Opin. Neurobiol 63, 59– 66. 32311648 PMC7483800
  19. Formentini L, Moroni F, and Chiarugi A (2009). Detection and pharmacological modulation of nicotinamide mononucleotide (NMN) in vitro and in vivo. Biochem. Pharmacol 77, 1612– 1620. 19426698
  20. Geisler S, Doan RA, Strickland A, Huang X, Milbrandt J, and DiAntonio A (2016). Prevention of vincristine-induced peripheral neuropathy by genetic deletion of SARM1 in mice. Brain 139, 3092– 3108. 27797810 PMC5840884
  21. Geisler S, Huang SX, Strickland A, Doan RA, Summers DW, Mao X, Park J, DiAntonio A, and Milbrandt J (2019). Gene therapy targeting SARM1 blocks pathological axon degeneration in mice. J. Exp. Med 216, 294– 303. 30642945 PMC6363435
  22. Gerdts J, Sasaki Y, Vohra B, Marasa J, and Milbrandt J (2011). Image-based screening identifies novel roles for IkappaB kinase and glycogen synthase kinase 3 in axonal degeneration. J. Biol. Chem 286, 28011– 28018. 21685387 PMC3151046
  23. Gerdts J, Summers DW, Sasaki Y, DiAntonio A, and Milbrandt J (2013). Sarm1-mediated axon degeneration requires both SAM and TIR interactions. J. Neurosci 33, 13569– 13580. 23946415 PMC3742939
  24. Gilley J, and Coleman MP (2010). Endogenous Nmnat2 is an essential survival factor for maintenance of healthy axons. PLoS Biol. 8, e1000300. 20126265 PMC2811159
  25. Gilley J, Orsomando G, Nascimento-Ferreira I, and Coleman MP (2015). Absence of SARM1 rescues development and survival of NMNAT2-deficient axons. Cell Rep. 10, 1974– 1981. 25818290 PMC4386025
  26. Gilley J, Ribchester RR, and Coleman MP (2017). Sarm1 Deletion, but Not Wld(S), Confers Lifelong Rescue in a Mouse Model of Severe Axonopathy. Cell Rep. 21, 10– 16. 28978465 PMC5640801
  27. Goddard TD, Huang CC, Meng EC, Pettersen EF, Couch GS, Morris JH, and Ferrin TE (2018). UCSF ChimeraX: Meeting modern challenges in visualization and analysis. Protein Sci. 27, 14– 25. 28710774 PMC5734306
  28. Gu W, Luo Z, Vonrhein C, Jia X, Ve T, Nanson JD, and Kobe B (2021). Crystal structure determination of the armadillo repeat domain of Drosophila SARM1 using MIRAS phasing. bioRxiv, 10.1101/2021.1101.1131.428505. PMC8488856 34605441 · DOI
  29. Henninger N, Bouley J, Sikoglu EM, An J, Moore CM, King JA, Bowser R, Freeman MR, and Brown RH Jr. (2016). Attenuated traumatic axonal injury and improved functional outcome after traumatic brain injury in mice lacking Sarm1. Brain 139, 1094– 1105. 26912636 PMC5006226
  30. Hikosaka K, (2014). Deficiency of nicotinamide mononucleotide adenylyltransferase 3 (nmnat3) causes hemolytic anemia by altering the glycolytic flow in mature erythrocytes. J. Biol. Chem 289, 14796– 14811. 24739386 PMC4031534
  31. Holm L (2020). Using Dali for Protein Structure Comparison. Methods Mol. Biol 2112, 29– 42. 32006276
  32. Horsefield S, (2019). NAD(+) cleavage activity by animal and plant TIR domains in cell death pathways. Science 365, 793– 799. 31439792
  33. Huber AH, Nelson WJ, and Weis WI (1997). Three-dimensional structure of the armadillo repeat region of beta-catenin. Cell 90, 871– 882. 9298899
  34. Hughes RO, Bosanac T, Mao X, Engber TM, DiAntonio A, Milbrandt J, Devraj R, and Krauss R (2021). Small Molecule SARM1 Inhibitors Recapitulate the SARM1(−/−) Phenotype and Allow Recovery of a Metastable Pool of Axons Fated to Degenerate. Cell Rep. 34, 108588. 33406435 PMC8179325
  35. Jiang Y, Liu T, Lee CH, Chang Q, Yang J, and Zhang Z (2020). The NAD(+)-mediated self-inhibition mechanism of pro-neurodegenerative SARM1. Nature 588, 658– 663. 33053563
  36. Kidmose RT, Juhl J, Nissen P, Boesen T, Karlsen JL, and Pedersen BP (2019). Namdinator - automatic molecular dynamics flexible fitting of structural models into cryo-EM and crystallography experimental maps. IUCrJ 6, 526– 531. PMC6608625 31316797
  37. Ko KW, Milbrandt J, and DiAntonio A (2020). SARM1 acts downstream of neuroinflammatory and necroptotic signaling to induce axon degeneration. J. Cell Biol 219. PMC7401797 32609299
  38. Kobe B, and Kajava AV (2000). When protein folding is simplified to protein coiling: the continuum of solenoid protein structures. Trends Biochem. Sci 25, 509– 515. 11050437
  39. Koziara KB, Stroet M, Malde AK, and Mark AE (2014). Testing and validation of the Automated Topology Builder (ATB) version 2.0: prediction of hydration free enthalpies. J. Comput. Aided Mol. Des 28, 221– 233. 24477799
  40. Krauss R, Bosanac T, Devraj R, Engber T, and Hughes RO (2020). Axons Matter: The Promise of Treating Neurodegenerative Disorders by Targeting SARM1-Mediated Axonal Degeneration. Trends Pharmacol. Sci 41, 281– 293. 32107050
  41. Krissinel E, and Henrick K (2007). Inference of macromolecular assemblies from crystalline state. J. Mol. Biol 372, 774– 797. 17681537
  42. Kunz AP, Allison JR, Geerke DP, Horta BA, Hunenberger PH, Riniker S, Schmid N, and van Gunsteren WF (2012). New functionalities in the GROMOS biomolecular simulation software. J. Comput. Chem 33, 340– 353. 22076815
  43. Laskowski RA, Jabłońska J, Pravda L, Vařeková RS, and Thornton JM (2018). PDBsum: Structural summaries of PDB entries. Protein Sci. 27, 129– 134. 28875543 PMC5734310
  44. Llobet Rosell A, and Neukomm LJ (2019). Axon death signalling in Wallerian degeneration among species and in disease. Open Biol 9, 190118. 31455157 PMC6731592
  45. Lois C, Hong EJ, Pease S, Brown EJ, and Baltimore D (2002). Germline transmission and tissue-specific expression of transgenes delivered by lentiviral vectors. Science 295, 868– 872. 11786607
  46. Loreto A, (2020). Potent activation of SARM1 by NMN analogue VMN underlies vacor neurotoxicity. bioRxiv, 10.1101/2020.1109.1118.304261. · DOI
  47. Loreto A, Di Stefano M, Gering M, and Conforti L (2015). Wallerian Degeneration Is Executed by an NMN-SARM1-Dependent Late Ca(2+) Influx but Only Modestly Influenced by Mitochondria. Cell Rep. 13, 2539– 2552. 26686637
  48. Loring HS, and Thompson PR (2020). Emergence of SARM1 as a Potential Therapeutic Target for Wallerian-type Diseases. Cell Chem Biol 27, 1– 13. 31761689 PMC6980728
  49. Ma S, (2020). Direct pathogen-induced assembly of an NLR immune receptor complex to form a holoenzyme. Science 370, eabe3069. 33273071
  50. Malde AK, Zuo L, Breeze M, Stroet M, Poger D, Nair PC, Oostenbrink C, and Mark AE (2011). An Automated Force Field Topology Builder (ATB) and Repository: Version 1.0. J. Chem. Theory Comput 7, 4026– 4037. 26598349
  51. Marion CM, McDaniel DP, and Armstrong RC (2019). Sarm1 deletion reduces axon damage, demyelination, and white matter atrophy after experimental traumatic brain injury. Exp. Neurol 321, 113040. 31445042
  52. Martin R, Qi T, Zhang H, Liu F, King M, Toth C, Nogales E, and Staskawicz BJ (2020). Structure of the activated ROQ1 resistosome directly recognizing the pathogen effector XopQ. Science 370, eabd9993. 33273074 PMC7995448
  53. Matsuura Y, and Stewart M (2004). Structural basis for the assembly of a nuclear export complex. Nature 432, 872– 877. 15602554
  54. Mayer M, and Meyer B (1999). Characterization of Ligand Binding by Saturation Transfer Difference NMR Spectroscopy. Angew. Chem. Int. Ed. Engl 38, 1784– 1788. 29711196
  55. Maynard ME, Redell JB, Zhao J, Hood KN, Vita SM, Kobori N, and Dash PK (2020). Sarm1 loss reduces axonal damage and improves cognitive outcome after repetitive mild closed head injury. Exp. Neurol 327, 113207. 31962129 PMC7959192
  56. McCoy AJ (2007). Solving structures of protein complexes by molecular replacement with Phaser. Acta Crystallogr. D Biol. Crystallogr 63, 32– 41. 17164524 PMC2483468
  57. Mehmel M, Jovanovic N, and Spitz U (2020). Nicotinamide Riboside-The Current State of Research and Therapeutic Uses. Nutrients 12. PMC7352172 32486488
  58. Notredame C, Higgins DG, and Heringa J (2000). T-Coffee: A novel method for fast and accurate multiple sequence alignment. J. Mol. Biol 302, 205– 217. 10964570
  59. Oostenbrink C, Villa A, Mark AE, and van Gunsteren WF (2004). A biomolecular force field based on the free enthalpy of hydration and solvation: the GROMOS force-field parameter sets 53A5 and 53A6. J. Comput. Chem 25, 1656– 1676. 15264259
  60. Osterloh JM, (2012). dSarm/Sarm1 is required for activation of an injury-induced axon death pathway. Science 337, 481– 484. 22678360 PMC5225956
  61. Park J, (2020). Quaternary structures of Vac8 differentially regulate the Cvt and PMN pathways. Autophagy 16, 991– 1006. 31512555 PMC7469494
  62. Pintilie GD, Zhang J, Goddard TD, Chiu W, and Gossard DC (2010). Quantitative analysis of cryo-EM density map segmentation by watershed and scale-space filtering, and fitting of structures by alignment to regions. J. Struct. Biol 170, 427– 438. 20338243 PMC2874196
  63. Piotto M, Saudek V, and Sklenar V (1992). Gradient-tailored excitation for single-quantum NMR spectroscopy of aqueous solutions. J. Biomol. NMR 2, 661– 665. 1490109
  64. Punjani A, Rubinstein JL, Fleet DJ, and Brubaker MA (2017). cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290– 296. 28165473
  65. Rosenthal PB, and Henderson R (2003). Optimal determination of particle orientation, absolute hand, and contrast loss in single-particle electron cryomicroscopy. J. Mol. Biol 333, 721– 745. 14568533
  66. Salomon-Ferrer R, Gotz AW, Poole D, Le Grand S, and Walker RC (2013). Routine Microsecond Molecular Dynamics Simulations with AMBER on GPUs. 2. Explicit Solvent Particle Mesh Ewald. J. Chem. Theory Comput 9, 3878– 3888. 26592383
  67. Sanchez-Garcia R, Gomez-Blanco J, Cuervo A, Carazo JM, Sorzano COS, and Vargas J (2020). DeepEMhancer: a deep learning solution for cryo-EM volume post-processing. bioRxiv, 10.1101/2020.1106.1112.148296. PMC8282847 34267316 · DOI
  68. Saridakis V, Christendat D, Kimber MS, Dharamsi A, Edwards AM, and Pai EF (2001). Insights into ligand binding and catalysis of a central step in NAD+ synthesis: structures of Methanobacterium thermoautotrophicum NMN adenylyltransferase complexes. J. Biol. Chem 276, 7225– 7232. 11063748
  69. Sasaki Y, (2020a). cADPR is a gene dosage-sensitive biomarker of SARM1 activity in healthy, compromised, and degenerating axons. Exp. Neurol 329, 113252. 32087251 PMC7302925
  70. Sasaki Y, (2020b). SARM1 depletion rescues NMNAT1-dependent photoreceptor cell death and retinal degeneration. Elife 9, e62027. 33107823 PMC7591247
  71. Sasaki Y, Nakagawa T, Mao X, DiAntonio A, and Milbrandt J (2016). NMNAT1 inhibits axon degeneration via blockade of SARM1-mediated NAD(+) depletion. Elife 5, e19749. 27735788 PMC5063586
  72. Sasaki Y, Vohra BP, Lund FE, and Milbrandt J (2009). Nicotinamide mononucleotide adenylyl transferase-mediated axonal protection requires enzymatic activity but not increased levels of neuronal nicotinamide adenine dinucleotide. J. Neurosci 29, 5525– 5535. 19403820 PMC3162248
  73. Scheres SH, and Chen S (2012). Prevention of overfitting in cryo-EM structure determination. Nat. Methods 9, 853– 854. 22842542 PMC4912033
  74. Schmid N, Eichenberger AP, Choutko A, Riniker S, Winger M, Mark AE, and van Gunsteren WF (2011). Definition and testing of the GROMOS force-field versions 54A7 and 54B7. Eur. Biophys. J 40, 843– 856. 21533652
  75. Shen C, (2021). Multiple domain interfaces mediate SARM1 autoinhibition. Proc. Natl. Acad. Sci. U. S. A 118, e2023151118. 33468661 PMC7848697
  76. Shimizu H, Toma-Fukai S, Saijo S, Shimizu N, Kontani K, Katada T, and Shimizu T (2017). Structure-based analysis of the guanine nucleotide exchange factor SmgGDS reveals armadillo-repeat motifs and key regions for activity and GTPase binding. J. Biol. Chem 292, 13441– 13448. 28630045 PMC5555202
  77. Sporny M, (2020). Structural basis for SARM1 inhibition and activation under energetic stress. Elife 9, e62021. 33185189 PMC7688312
  78. Sporny M, Guez-Haddad J, Lebendiker M, Ulisse V, Volf A, Mim C, Isupov MN, and Opatowsky Y (2019). Structural Evidence for an Octameric Ring Arrangement of SARM1. J. Mol. Biol 431, 3591– 3605. 31278906
  79. Stewart SA, (2003). Lentivirus-delivered stable gene silencing by RNAi in primary cells. RNA 9, 493– 501. 12649500 PMC1370415
  80. Stols L, Gu M, Dieckman L, Raffen R, Collart FR, and Donnelly MI (2002). A new vector for high-throughput, ligation-independent cloning encoding a tobacco etch virus protease cleavage site. Protein Expr. Purif 25, 8– 15. 12071693
  81. Stroet M, Caron B, Visscher KM, Geerke DP, Malde AK, and Mark AE (2018). Automated Topology Builder Version 3.0: Prediction of Solvation Free Enthalpies in Water and Hexane. J. Chem. Theory Comput 14, 5834– 5845. 30289710
  82. Studier FW (2005). Protein production by auto-induction in high-density shaking cultures. Protein Expr. Purif 41, 207– 234. 15915565
  83. Summers DW, Gibson DA, DiAntonio A, and Milbrandt J (2016). SARM1-specific motifs in the TIR domain enable NAD+ loss and regulate injury-induced SARM1 activation. Proc. Natl. Acad. Sci. U. S. A 113, E6271– E6280. 27671644 PMC5068253
  84. Sun J, Siroy A, Lokareddy RK, Speer A, Doornbos KS, Cingolani G, and Niederweis M (2015). The tuberculosis necrotizing toxin kills macrophages by hydrolyzing NAD. Nat. Struct. Mol. Biol 22, 672– 678. 26237511 PMC4560639
  85. Szretter KJ, Samuel MA, Gilfillan S, Fuchs A, Colonna M, and Diamond MS (2009). The immune adaptor molecule SARM modulates tumor necrosis factor alpha production and microglia activation in the brainstem and restricts West Nile Virus pathogenesis. J. Virol 83, 9329– 9338. 19587044 PMC2738257
  86. Tak U, Vlach J, Garza-Garcia A, William D, Danilchanka O, de Carvalho LPS, Saad JS, and Niederweis M (2019). The tuberculosis necrotizing toxin is an NAD(+) and NADP(+) glycohydrolase with distinct enzymatic properties. J. Biol. Chem 294, 3024– 3036. 30593509 PMC6398120
  87. Tewari R, Bailes E, Bunting KA, and Coates JC (2010). Armadillo-repeat protein functions: questions for little creatures. Trends Cell Biol. 20, 470– 481. 20688255
  88. Turkiew E, Falconer D, Reed N, and Hoke A (2017). Deletion of Sarm1 gene is neuroprotective in two models of peripheral neuropathy. J. Peripher. Nerv. Syst 22, 162– 171. 28485482 PMC5585053
  89. Vonrhein C, Blanc E, Roversi P, and Bricogne G (2007). Automated structure solution with autoSHARP. Methods Mol. Biol 364, 215– 230. 17172768
  90. Vonrhein C, Flensburg C, Keller P, Sharff A, Smart O, Paciorek W, Womack T, and Bricogne G (2011). Data processing and analysis with the autoPROC toolbox. Acta Crystallogr. D Biol. Crystallogr 67, 293– 302. 21460447 PMC3069744
  91. Wallace AC, Laskowski RA, and Thornton JM (1995). LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. Protein Eng. 8, 127– 134. 7630882
  92. Wan L, (2019). TIR domains of plant immune receptors are NAD(+)-cleaving enzymes that promote cell death. Science 365, 799– 803. 31439793 PMC7045805
  93. Webb B, and Sali A (2016). Comparative Protein Structure Modeling Using MODELLER. Curr Protoc Bioinformatics 54, 5.6.1– 5.6.37. 27322406 PMC5031415
  94. Williams CJ, (2018). MolProbity: More and better reference data for improved all-atom structure validation. Protein Sci. 27, 293– 315. 29067766 PMC5734394
  95. Zhao ZY, (2019). A Cell-Permeant Mimetic of NMN Activates SARM1 to Produce Cyclic ADP-Ribose and Induce Non-apoptotic Cell Death. iScience 15, 452– 466. 31128467 PMC6531917
  96. Zhou T, Kurnasov O, Tomchick DR, Binns DD, Grishin NV, Marquez VE, Osterman AL, and Zhang H (2002). Structure of Human Nicotinamide/Nicotinic Acid Mononucleotide Adenylyltransferase: Basis for the dual substrate specificity and activation of the oncolytic agent tiazofurin. J. Biol. Chem 277, 13148– 13154. 11788603
  97. Ziogas NK, and Koliatsos VE (2018). Primary Traumatic Axonopathy in Mice Subjected to Impact Acceleration: A Reappraisal of Pathology and Mechanisms with High-Resolution Anatomical Methods. J. Neurosci 38, 4031– 4047. 29567804 PMC6705930

Cited by

Sorted by citations

Authors
Figley, M. D., Gu, W., Nanson, J. D., Shi, Y., Sasaki, Y., Cunnea, K., Malde, A. K., Jia, X., Luo, Z., Saikot, F. K., Mosaiab, T., Masic, V., Holt, S., Hartley-Tassell, L., McGuinness, H. Y., Manik, M. K., Bosanac, T., Landsberg, M. J., Kerry, P. S., Mobli, M., Hughes, R. O., Milbrandt, J., Kobe, B., DiAntonio, A., & Ve, T.
Affiliations
  • Washington University in St. Louis (US)
  • The University of Queensland (AU)
  • Griffith University (AU)
  • Evotec (Germany) (DE)
  • Disarm Therapeutics (United States) (US)
Corresponding author
  • Milbrandt, Jeffrey
  • DiAntonio, Aaron
  • Ve, Thomas
ORCID
Venue
Neuron
Publisher
Elsevier BV
Published
2021-04
Volume
109
Issue
7
Pages
1118-1136.e11
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2021.02.009
PMC
PMC8174188
OpenAlex
W3133905451
Cited by
324
References
4
Citations by year
2026: 40 · 2025: 68 · 2024: 48 · 2023: 56 · 2022: 61 · 2021: 49 · 2020: 1
FWCI
29.91
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Griffith Research Online (submittedVersion, other-oa)
Funders
  • National Computational Infrastructure (cj47)
  • National Institutes of Health (R01CA219866, RF1AG013730, RO1NS087632)
  • National Health and Medical Research Council (1107804, 1071659, 1160570, 1108859)
  • National Institute of Health and Medical Research (RO1NS087632, R01CA219866, RF1AG013730)
  • Queensland Cyber Infrastructure Foundation (fi49)
  • Australian Research Council (FL180100109)
  • University of Queensland
Topics
  • Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords
SARM1, axonal degeneration, metabolic sensors, NAD+ metabolism, neurodegeneration
MeSH terms
Animals, Axons, Cytoskeletal Proteins, Enzyme Activation, Humans, Models, Molecular, NAD, Nerve Degeneration, Nicotinamide Mononucleotide, Nicotinamide-Nucleotide Adenylyltransferase, Protein Conformation, Mutagenesis, Mice, Knockout, Armadillo Domain Proteins, Mice, Molecular Dynamics Simulation, HEK293 Cells

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