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We hypothesized that supplementing NAD+ precursors could alleviate DPN symptoms through increasing the NAD+ levels and activating the sirtuin-1 (SIRT1) protein. To test this, we exposed cultured Dorsal Root Ganglion neurons (DRGs) to Nicotinamide Riboside (NR) or Nicotinamide Mononucleotide (NMN), which increased the levels of NAD+, the SIRT1 protein, and the deacetylation activity that is associated with increased neurite growth. A SIRT1 inhibitor blocked the neurite growth induced via NR or NMN. We then induced neuropathy in C57BL6 mice with streptozotocin (STZ) or a high fat diet (HFD) and administered NR or NMN for two months. Both the STZ and HFD mice developed neuropathy, which was reversed through the NR or NMN administration: sensory function improved, nerve conduction velocities normalized, and intraepidermal nerve fibers were restored. The NAD+ levels and SIRT1 activity were reduced in the DRGs from diabetic mice but were preserved with the NR or NMN treatment. We also tested the effect of NR or NMN administration in mice that overexpress the SIRT1 protein in neurons (nSIRT1 OE) and found no additional benefit from the addition of the drug. These findings suggest that supplementing with NAD+ precursors or activating SIRT1 may be a promising treatment for DPN.<\/jats:p>","DOI":"10.3390\/ijms25021102","type":"journal-article","created":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T08:12:37Z","timestamp":1705392757000},"page":"1102","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["NAD+ Precursors Reverse Experimental Diabetic Neuropathy in Mice"],"prefix":"10.3390","volume":"25","author":[{"given":"Krish","family":"Chandrasekaran","sequence":"first","affiliation":[{"name":"Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neda","family":"Najimi","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avinash R.","family":"Sagi","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushuma","family":"Yarlagadda","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Salimian","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammed Ikbal","family":"Arvas","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad F.","family":"Hedayat","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanni","family":"Kevas","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anand","family":"Kadakia","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1804-8999","authenticated-orcid":false,"given":"Tibor","family":"Kristian","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"},{"name":"Veterans Affairs Medical Center, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8940-8920","authenticated-orcid":false,"given":"James W.","family":"Russell","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"},{"name":"Veterans Affairs Medical Center, Baltimore, MD 21201, USA"},{"name":"CAMC Institute for Academic Medicine, 415 Morris Street Suite 300, Charleston, WV 25301, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Chandrasekaran, K., Najimi, N., Sagi, A.R., Yarlagadda, S., Salimian, M., Arvas, M.I., Hedayat, A.F., Kevas, Y., Kadakia, A., and Russell, J.W. (2022). NAD(+) Precursors Repair Mitochondrial Function in Diabetes and Prevent Experimental Diabetic Neuropathy. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094887"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Chandrasekaran, K., Choi, J., Arvas, M.I., Salimian, M., Singh, S., Xu, S., Gullapalli, R.P., Kristian, T., and Russell, J.W. (2020). Nicotinamide Mononucleotide Administration Prevents Experimental Diabetes-Induced Cognitive Impairment and Loss of Hippocampal Neurons. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21113756"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3737","DOI":"10.1093\/brain\/awz324","article-title":"Overexpression of Sirtuin 1 protein in neurons prevents and reverses experimental diabetic neuropathy","volume":"142","author":"Chandrasekaran","year":"2019","journal-title":"Brain"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"26933","DOI":"10.1038\/srep26933","article-title":"Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice","volume":"6","author":"Trammell","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/bs.irn.2019.04.002","article-title":"Role of mitochondria in diabetic peripheral neuropathy: Influencing the NAD(+)-dependent SIRT1-PGC-1alpha-TFAM pathway","volume":"145","author":"Chandrasekaran","year":"2016","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/j.molmed.2017.08.001","article-title":"NAD(+) in Aging: Molecular Mechanisms and Translational Implications","volume":"23","author":"Fang","year":"2017","journal-title":"Trends Mol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.cmet.2017.11.002","article-title":"NAD(+) Intermediates: The Biology and Therapeutic Potential of NMN and NR","volume":"27","author":"Yoshino","year":"2018","journal-title":"Cell Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.neuron.2015.12.023","article-title":"Axon Self-Destruction: New Links among SARM1, MAPKs, and NAD+ Metabolism","volume":"89","author":"Gerdts","year":"2016","journal-title":"Neuron"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/s41583-020-0269-3","article-title":"Programmed axon degeneration: From mouse to mechanism to medicine","volume":"21","author":"Coleman","year":"2020","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"397","DOI":"10.3109\/10409238.2013.789479","article-title":"NAD\u207a metabolism: A therapeutic target for age-related metabolic disease","volume":"48","author":"Mouchiroud","year":"2013","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1016\/j.bbapap.2016.06.014","article-title":"NAD(+) metabolism: Bioenergetics, signaling and manipulation for therapy","volume":"1864","author":"Yang","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1126\/science.1223899","article-title":"dSarm\/Sarm1 is required for activation of an injury-induced axon death pathway","volume":"337","author":"Osterloh","year":"2012","journal-title":"Science"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3092","DOI":"10.1093\/brain\/aww251","article-title":"Prevention of vincristine-induced peripheral neuropathy by genetic deletion of SARM1 in mice","volume":"139","author":"Geisler","year":"2016","journal-title":"Brain"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1111\/jns.12219","article-title":"Deletion of Sarm1 gene is neuroprotective in two models of peripheral neuropathy","volume":"22","author":"Turkiew","year":"2017","journal-title":"J. Peripher. Nerv. Syst."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.neures.2018.07.001","article-title":"Metabolic aspects of neuronal degeneration: From a NAD(+) point of view","volume":"139","author":"Sasaki","year":"2019","journal-title":"Neurosci. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3629","DOI":"10.1096\/fj.07-8290com","article-title":"The enzyme CD38 (a NAD glycohydrolase, EC 3.2.2.5) is necessary for the development of diet-induced obesity","volume":"21","author":"Barbosa","year":"2007","journal-title":"FASEB J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1016\/j.freeradbiomed.2007.09.013","article-title":"PARP inhibition or gene deficiency counteracts intraepidermal nerve fiber loss and neuropathic pain in advanced diabetic neuropathy","volume":"44","author":"Obrosova","year":"2008","journal-title":"Free Radic. Biol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.bbrc.2006.08.066","article-title":"Regulation of SIRT 1 mediated NAD dependent deacetylation: A novel role for the multifunctional enzyme CD38","volume":"349","author":"Aksoy","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1089\/ars.2023.0350","article-title":"NAD(+), Axonal Maintenance, and Neurological Disease","volume":"39","author":"Alexandris","year":"2023","journal-title":"Antioxid. Redox Signal."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1016\/j.cub.2017.01.070","article-title":"NMN Deamidase Delays Wallerian Degeneration and Rescues Axonal Defects Caused by NMNAT2 Deficiency In Vivo","volume":"27","author":"Loreto","year":"2017","journal-title":"Curr. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1126\/science.1098014","article-title":"Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration","volume":"305","author":"Araki","year":"2004","journal-title":"Science"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"14178","DOI":"10.1073\/pnas.250422697","article-title":"Silent information regulator 2 family of NAD- dependent histone\/protein deacetylases generates a unique product, 1-O-acetyl-ADP-ribose","volume":"97","author":"Tanner","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"50985","DOI":"10.1074\/jbc.M306552200","article-title":"Mechanism of nicotinamide inhibition and transglycosidation by Sir2 histone\/protein deacetylases","volume":"278","author":"Jackson","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/nrendo.2011.225","article-title":"Sirtuins mediate mammalian metabolic responses to nutrient availability","volume":"8","author":"Chalkiadaki","year":"2012","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1146\/annurev-pharmtox-010611-134657","article-title":"Small-molecule allosteric activators of sirtuins","volume":"54","author":"Sinclair","year":"2014","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/s10286-019-00607-x","article-title":"Physical activity and dietary interventions in diabetic neuropathy: A systematic review","volume":"4","author":"Zilliox","year":"2019","journal-title":"Clin. Auton. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/978-1-4939-9434-2_8","article-title":"Molecular and Cellular Characterization of SIRT1 Allosteric Activators","volume":"1983","author":"Schultz","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"53","DOI":"10.3389\/fnagi.2013.00053","article-title":"Sirtuins in neurodegenerative diseases: An update on potential mechanisms","volume":"5","author":"Min","year":"2013","journal-title":"Front. Aging Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1002\/emmm.201302451","article-title":"SIRT1 and SIRT2: Emerging targets in neurodegeneration","volume":"5","author":"Donmez","year":"2013","journal-title":"EMBO Mol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"12613","DOI":"10.1038\/srep12613","article-title":"Sirt1-deficiency causes defective protein quality control","volume":"5","author":"Tomita","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"9989","DOI":"10.1523\/JNEUROSCI.3257-08.2008","article-title":"Brain SIRT1: Anatomical distribution and regulation by energy availability","volume":"28","author":"Ramadori","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/s42255-018-0009-4","article-title":"Slc12a8 is a nicotinamide mononucleotide transporter","volume":"1","author":"Grozio","year":"2019","journal-title":"Nat. Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1016\/j.cmet.2012.04.022","article-title":"The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity","volume":"15","author":"Canto","year":"2012","journal-title":"Cell Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1111\/dom.12171","article-title":"The importance of NAMPT\/NAD\/SIRT1 in the systemic regulation of metabolism and ageing","volume":"15","author":"Imai","year":"2013","journal-title":"Diabetes Obes. Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1016\/j.cmet.2011.08.014","article-title":"Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice","volume":"14","author":"Yoshino","year":"2011","journal-title":"Cell Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1111\/cns.12539","article-title":"Targeting Nicotinamide Phosphoribosyltransferase as a Potential Therapeutic Strategy to Restore Adult Neurogenesis","volume":"22","author":"Wang","year":"2016","journal-title":"CNS Neurosci. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/cdd.2014.164","article-title":"A rise in NAD precursor nicotinamide mononucleotide (NMN) after injury promotes axon degeneration","volume":"22","author":"Orsomando","year":"2015","journal-title":"Cell Death Differ."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Li, W., Gao, M., Hu, C., Chen, X., and Zhou, Y. (2023). NMNAT2: An important metabolic enzyme affecting the disease progression. Biomed. Pharmacother., 158.","DOI":"10.1016\/j.biopha.2022.114143"},{"key":"ref_39","first-page":"3373","article-title":"Nicotinamide mononucleotide adenylyltransferase 1 gene NMNAT1 regulates neuronal dendrite and axon morphogenesis in vitro","volume":"124","author":"Zhao","year":"2011","journal-title":"Chin. Med. J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2567","DOI":"10.1038\/srep02567","article-title":"Deletions within its subcellular targeting domain enhance the axon protective capacity of Nmnat2 in vivo","volume":"3","author":"Milde","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1007\/s12017-009-8058-1","article-title":"Nicotinamide prevents NAD+ depletion and protects neurons against excitotoxicity and cerebral ischemia: NAD+ consumption by SIRT1 may endanger energetically compromised neurons","volume":"11","author":"Liu","year":"2009","journal-title":"Neuromolecular Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.neuron.2010.01.028","article-title":"Nedd4 branches out","volume":"65","author":"DiAntonio","year":"2010","journal-title":"Neuron"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.4161\/cc.9.13.12236","article-title":"The ubiquitin E3 ligase Nedd4-1 controls neurite development","volume":"9","author":"Kawabe","year":"2010","journal-title":"Cell Cycle"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.neuron.2010.01.007","article-title":"Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development","volume":"65","author":"Kawabe","year":"2010","journal-title":"Neuron"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"13205","DOI":"10.1073\/pnas.1400737111","article-title":"Ubiquitin E3 ligase Nedd4-1 acts as a downstream target of PI3K\/PTEN-mTORC1 signaling to promote neurite growth","volume":"111","author":"Hsia","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"8585","DOI":"10.1073\/pnas.0803233105","article-title":"The ubiquitin ligase Nedd4-1 is dispensable for the regulation of PTEN stability and localization","volume":"105","author":"Fouladkou","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.cell.2006.11.039","article-title":"NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN","volume":"128","author":"Wang","year":"2007","journal-title":"Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"140","DOI":"10.2174\/156652413804486241","article-title":"Extranuclear localization of SIRT1 and PGC-1alpha: An insight into possible roles in diseases associated with mitochondrial dysfunction","volume":"13","author":"Aquilano","year":"2013","journal-title":"Curr. Mol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"21590","DOI":"10.1074\/jbc.M109.070169","article-title":"Peroxisome proliferator-activated receptor gamma co-activator 1alpha (PGC-1alpha) and sirtuin 1 (SIRT1) reside in mitochondria: Possible direct function in mitochondrial biogenesis","volume":"285","author":"Aquilano","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1146\/annurev-biochem-060310-170328","article-title":"The ubiquitin code","volume":"81","author":"Komander","year":"2012","journal-title":"Annu. Rev. Biochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.ydbio.2009.03.023","article-title":"Abnormal development of the neuromuscular junction in Nedd4-deficient mice","volume":"330","author":"Liu","year":"2009","journal-title":"Dev. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/1749-8104-8-18","article-title":"The Nedd4-binding protein 3 (N4BP3) is crucial for axonal and dendritic branching in developing neurons","volume":"8","author":"Schmeisser","year":"2013","journal-title":"Neural Dev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.neuron.2010.01.017","article-title":"E3 ligase Nedd4 promotes axon branching by downregulating PTEN","volume":"65","author":"Drinjakovic","year":"2010","journal-title":"Neuron"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.mcn.2012.04.006","article-title":"Disruption of E3 ligase NEDD4 in peripheral neurons interrupts axon outgrowth: Linkage to PTEN","volume":"50","author":"Christie","year":"2012","journal-title":"Mol. Cell Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1093\/hmg\/ddv445","article-title":"NEDD4-mediated HSF1 degradation underlies alpha-synucleinopathy","volume":"25","author":"Kim","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1038\/s41419-019-2142-8","article-title":"The many substrates and functions of NEDD4-1","volume":"10","author":"Huang","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2807","DOI":"10.1016\/j.celrep.2020.01.088","article-title":"Auto-ubiquitination of NEDD4-1 Recruits USP13 to Facilitate Autophagy through Deubiquitinating VPS34","volume":"30","author":"Xie","year":"2020","journal-title":"Cell Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.celrep.2017.09.027","article-title":"Sarm1 Deletion, but Not Wld(S), Confers Lifelong Rescue in a Mouse Model of Severe Axonopathy","volume":"21","author":"Gilley","year":"2017","journal-title":"Cell Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1016\/j.celrep.2015.02.060","article-title":"Absence of SARM1 rescues development and survival of NMNAT2-deficient axons","volume":"10","author":"Gilley","year":"2015","journal-title":"Cell Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"113040","DOI":"10.1016\/j.expneurol.2019.113040","article-title":"Sarm1 deletion reduces axon damage, demyelination, and white matter atrophy after experimental traumatic brain injury","volume":"321","author":"Marion","year":"2019","journal-title":"Exp. Neurol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"7337","DOI":"10.1007\/s12035-022-03050-8","article-title":"Mitochondrial Localization of SARM1 in Acrylamide Intoxication Induces Mitophagy and Limits Neuropathy","volume":"59","author":"Wang","year":"2022","journal-title":"Mol. Neurobiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"133","DOI":"10.4161\/bioa.27049","article-title":"Axonal trafficking of NMNAT2 and its roles in axon growth and survival in vivo","volume":"3","author":"Milde","year":"2013","journal-title":"Bioarchitecture"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Yang, S., Niou, Z.X., Enriquez, A., LaMar, J., Huang, J.Y., Ling, K., Jafar-Nejad, P., Gilley, J., Coleman, M.P., and Tennessen, J.M. (2023). NMNAT2 supports vesicular glycolysis via NAD homeostasis to fuel fast axonal transport. Res. Sq.","DOI":"10.21203\/rs.3.rs-2859584\/v1"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Luchniak, A., Mahamdeh, M., and Howard, J. (2019). Nicotinamide adenine dinucleotides and their precursor NMN have no direct effect on microtubule dynamics in purified brain tubulin. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0220794"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/s41572-019-0092-1","article-title":"Diabetic neuropathy","volume":"5","author":"Feldman","year":"2019","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/j.1472-8206.2007.00530.x","article-title":"Nicotinic acid in the treatment of hyperlipidaemia","volume":"21","author":"Drexel","year":"2007","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1093\/ajcn\/nqy132","article-title":"A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: Safety, insulin-sensitivity, and lipid-mobilizing effects","volume":"108","author":"Dollerup","year":"2018","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.cmet.2009.02.006","article-title":"Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation","volume":"9","author":"Purushotham","year":"2009","journal-title":"Cell Metab."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ymgmr.2017.05.003","article-title":"Resveratrol attenuates triglyceride accumulation associated with upregulation of Sirt1 and lipoprotein lipase in 3T3-L1 adipocytes","volume":"12","author":"Imamura","year":"2017","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s12986-022-00653-9","article-title":"Effects of NAD+ precursor supplementation on glucose and lipid metabolism in humans: A meta-analysis","volume":"19","author":"Zhong","year":"2022","journal-title":"Nutr. Metab."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1002\/hep.28245","article-title":"Eliciting the mitochondrial unfolded protein response by nicotinamide adenine dinucleotide repletion reverses fatty liver disease in mice","volume":"63","author":"Gariani","year":"2016","journal-title":"Hepatology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.nbd.2014.01.001","article-title":"PGC-1\u03b1 regulation of mitochondrial degeneration in experimental diabetic neuropathy","volume":"64","author":"Choi","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"E132","DOI":"10.1152\/ajpendo.00620.2014","article-title":"Mitochondrial transcription factor A regulation of mitochondrial degeneration in experimental diabetic neuropathy","volume":"309","author":"Chandrasekaran","year":"2015","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.4155\/bio.14.8","article-title":"Measuring NAD(+) levels in mouse blood and tissue samples via a surrogate matrix approach using LC-MS\/MS","volume":"6","author":"Liang","year":"2014","journal-title":"Bioanalysis"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1111\/jns5.12072","article-title":"Phenotyping animal models of diabetic neuropathy: A consensus statement of the diabetic neuropathy study group of the EASD (Neurodiab)","volume":"19","author":"Biessels","year":"2014","journal-title":"J. Peripher. Nerv. Syst."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1002\/acn3.484","article-title":"mGluR2\/3 activation of the SIRT1 axis preserves mitochondrial function in diabetic neuropathy","volume":"4","author":"Chandrasekaran","year":"2017","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1111\/j.1468-1331.2010.03023.x","article-title":"European Federation of Neurological Societies\/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society","volume":"17","author":"Lauria","year":"2010","journal-title":"Eur. J. Neurol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1111\/j.1468-1331.2005.01260.x","article-title":"EFNS guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy","volume":"12","author":"Lauria","year":"2005","journal-title":"Eur. J. Neurol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.nbd.2008.02.013","article-title":"Oxidative injury and neuropathy in diabetes and impaired glucose tolerance","volume":"30","author":"Russell","year":"2008","journal-title":"Neurobiol. Dis."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/2\/1102\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:48:07Z","timestamp":1760104087000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/2\/1102"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,16]]},"references-count":79,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["ijms25021102"],"URL":"https:\/\/doi.org\/10.3390\/ijms25021102","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,16]]}}}