{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T03:08:00Z","timestamp":1773371280325,"version":"3.50.1"},"reference-count":60,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,6,23]],"date-time":"2024-06-23T00:00:00Z","timestamp":1719100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG078181"],"award-info":[{"award-number":["R01AG078181"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["90108172"],"award-info":[{"award-number":["90108172"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"JHU Merkin PNNR Center","award":["R01AG078181"],"award-info":[{"award-number":["R01AG078181"]}]},{"name":"JHU Merkin PNNR Center","award":["90108172"],"award-info":[{"award-number":["90108172"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Peripheral nerve injuries (PNIs) represent a significant clinical challenge, particularly in elderly populations where axonal remyelination and regeneration are impaired. Developing therapies to enhance these processes is crucial for improving PNI repair outcomes. Glutamate carboxypeptidase II (GCPII) is a neuropeptidase that plays a pivotal role in modulating glutamate signaling through its enzymatic cleavage of the abundant neuropeptide N-acetyl aspartyl glutamate (NAAG) to liberate glutamate. Within the PNS, GCPII is expressed in Schwann cells and activated macrophages, and its expression is amplified with aging. In this study, we explored the therapeutic potential of inhibiting GCPII activity following PNI. We report significant GCPII protein and activity upregulation following PNI, which was normalized by the potent and selective GCPII inhibitor 2-(phosphonomethyl)-pentanedioic acid (2-PMPA). In vitro, 2-PMPA robustly enhanced myelination in dorsal root ganglion (DRG) explants. In vivo, using a sciatic nerve crush injury model in aged mice, 2-PMPA accelerated remyelination, as evidenced by increased myelin sheath thickness and higher numbers of remyelinated axons. These findings suggest that GCPII inhibition may be a promising therapeutic strategy to enhance remyelination and potentially improve functional recovery after PNI, which is especially relevant in elderly PNI patients where this process is compromised.<\/jats:p>","DOI":"10.3390\/ijms25136893","type":"journal-article","created":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T08:42:03Z","timestamp":1719218523000},"page":"6893","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["GCPII Inhibition Promotes Remyelination after Peripheral Nerve Injury in Aged Mice"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3171-4690","authenticated-orcid":false,"given":"Yu","family":"Su","sequence":"first","affiliation":[{"name":"Johns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meixiang","family":"Huang","sequence":"additional","affiliation":[{"name":"Johns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ajit G.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Johns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Maragakis","sequence":"additional","affiliation":[{"name":"Johns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaitlyn D. 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Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3344","DOI":"10.1038\/s41598-022-07253-w","article-title":"Novel Roles of Phentolamine in Protecting Axon Myelination, Muscle Atrophy, and Functional Recovery Following Nerve Injury","volume":"12","author":"Zainul","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/0014-4886(80)90006-0","article-title":"Effects of Aging on Nerve Sprouting and Regeneration","volume":"70","author":"Pestronk","year":"1980","journal-title":"Exp. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1111\/j.1529-8027.2000.00026.x","article-title":"Influence of Aging on Peripheral Nerve Function and Regeneration","volume":"5","author":"Ceballos","year":"2000","journal-title":"J. Peripher. Nerv. Syst."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"963689720926157","DOI":"10.1177\/0963689720926157","article-title":"RNA Sequencing of Human Peripheral Nerve in Response to Injury: Distinctive Analysis of the Nerve Repair Pathways","volume":"29","author":"Welleford","year":"2020","journal-title":"Cell Transpl."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e62232","DOI":"10.7554\/eLife.62232","article-title":"Failures of Nerve Regeneration Caused by Aging or Chronic Denervation Are Rescued by Restoring Schwann Cell C-Jun","volume":"10","author":"Wagstaff","year":"2021","journal-title":"Elife"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"106330","DOI":"10.1016\/j.intimp.2020.106330","article-title":"An Effective Erythropoietin Dose Regimen Protects against Severe Nerve Injury-Induced Pathophysiological Changes with Improved Neural Gene Expression and Enhances Functional Recovery","volume":"82","author":"Govindappa","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"439","DOI":"10.4103\/1673-5374.346456","article-title":"Functional Recovery and Muscle Atrophy in Pre-Clinical Models of Peripheral Nerve Transection and Gap-Grafting in Mice: Effects of 4-Aminopyridine","volume":"18","author":"Lee","year":"2023","journal-title":"Neural Regen. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1093\/milmed\/usy399","article-title":"4-Aminopyridine as a Single Agent Diagnostic and Treatment for Severe Nerve Crush Injury","volume":"184","author":"Noble","year":"2019","journal-title":"Mil. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"19480","DOI":"10.1523\/JNEUROSCI.4067-13.2013","article-title":"Motor Axon Regeneration and Muscle Reinnervation in Young Adult and Aged Animals","volume":"33","author":"Kang","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.neuron.2014.06.016","article-title":"Diminished Schwann Cell Repair Responses Underlie Age-Associated Impaired Axonal Regeneration","volume":"83","author":"Painter","year":"2014","journal-title":"Neuron"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.1016\/j.celrep.2018.08.004","article-title":"Macrophages Regulate Schwann Cell Maturation after Nerve Injury","volume":"24","author":"Stratton","year":"2018","journal-title":"Cell Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"174","DOI":"10.3389\/fnagi.2020.00174","article-title":"Macrophages and Associated Ligands in the Aged Injured Nerve: A Defective Dynamic That Contributes to Reduced Axonal Regrowth","volume":"12","author":"Stratton","year":"2020","journal-title":"Front. Aging Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"103590","DOI":"10.1016\/j.mcn.2021.103590","article-title":"Macrophage Roles in Peripheral Nervous System Injury and Pathology: Allies in Neuromuscular Junction Recovery","volume":"111","author":"Rios","year":"2021","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e12833","DOI":"10.1111\/acel.12833","article-title":"Inflammaging Impairs Peripheral Nerve Maintenance and Regeneration","volume":"17","author":"Schulz","year":"2018","journal-title":"Aging Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1002\/jnr.24538","article-title":"Peripheral Nerve Injury and Myelination: Potential Therapeutic Strategies","volume":"98","author":"Modrak","year":"2020","journal-title":"J. Neurosci. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.hcl.2013.04.002","article-title":"Nerve Physiology","volume":"29","author":"Menorca","year":"2013","journal-title":"Hand Clin."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3521","DOI":"10.1113\/JP270874","article-title":"The Repair Schwann Cell and Its Function in Regenerating Nerves","volume":"594","author":"Jessen","year":"2016","journal-title":"J. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Baloyannis, S.J., Rossi, F.H., and Liu, W. (2022). Schwann Cell Plasticity in Peripheral Nerve Regeneration after Injury. Demyelination Disorders, IntechOpen.","DOI":"10.5772\/intechopen.90989"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3977","DOI":"10.1007\/s00018-020-03516-9","article-title":"Mechanisms of Schwann Cell Plasticity Involved in Peripheral Nerve Repair after Injury","volume":"77","author":"Nocera","year":"2020","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e17907","DOI":"10.15252\/emmm.202317907","article-title":"Senescent Schwann Cells Induced by Aging and Chronic Denervation Impair Axonal Regeneration Following Peripheral Nerve Injury","volume":"15","author":"Girardi","year":"2023","journal-title":"EMBO Mol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Wu, G., Wen, X., Kuang, R., Lui, K.W., He, B., Li, G., and Zhu, Z. (2024). Roles of Macrophages and Their Interactions with Schwann Cells after Peripheral Nerve Injury. Cell Mol. Neurobiol., 44.","DOI":"10.1007\/s10571-023-01442-5"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1186\/s12974-023-02929-0","article-title":"Deletion of CD47 from Schwann Cells and Macrophages Hastens Myelin Disruption\/Dismantling and Scavenging in Schwann Cells and Augments Myelin Debris Phagocytosis in Macrophages","volume":"20","author":"Gitik","year":"2023","journal-title":"J. Neuroinflamm."},{"key":"ref_24","first-page":"e56322","article-title":"In Vitro Phagocytosis of Myelin Debris by Bone Marrow-Derived Macrophages","volume":"130","author":"Rolfe","year":"2017","journal-title":"J. Vis. Exp."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nrn2054","article-title":"The Neuropoietic Cytokine Family in Development, Plasticity, Disease and Injury","volume":"8","author":"Bauer","year":"2007","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/1742-2094-8-109","article-title":"Wallerian Degeneration: The Innate-Immune Response to Traumatic Nerve Injury","volume":"8","author":"Rotshenker","year":"2011","journal-title":"J. Neuroinflamm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1111\/j.1471-4159.2011.07338.x","article-title":"Advances in Understanding the Peptide Neurotransmitter NAAG and Appearance of a New Member of the NAAG Neuropeptide Family","volume":"118","author":"Neale","year":"2011","journal-title":"J. Neurochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4491","DOI":"10.1096\/fj.09-148825","article-title":"Glutamate Carboxypeptidase II: An Amyloid Peptide-degrading Enzyme with Physiological Function in the Brain","volume":"24","author":"Kim","year":"2010","journal-title":"FASEB J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"21297","DOI":"10.1016\/S0021-9258(17)45359-2","article-title":"Rat Brain N-Acetylated Alpha-Linked Acidic Dipeptidase Activity. Purification and Immunologic Characterization","volume":"265","author":"Slusher","year":"1990","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/0306-4522(95)92578-8","article-title":"The Immunocytochemical Localization of N-Acetylaspartyl Glutamate, Its Hydrolysing Enzyme NAALADase, and the NMDAR-1 Receptor at a Vertebrate Neuromuscular Junction","volume":"64","author":"Berger","year":"1995","journal-title":"Neuroscience"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.nbd.2016.06.010","article-title":"Maternal Inflammation Leads to Impaired Glutamate Homeostasis and Up-Regulation of Glutamate Carboxypeptidase II in Activated Microglia in the Fetal\/Newborn Rabbit Brain","volume":"94","author":"Zhang","year":"2016","journal-title":"Neurobiol. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1007\/s13311-021-01159-7","article-title":"Dendrimer-2PMPA Delays Muscle Function Loss and Denervation in a Murine Model of Amyotrophic Lateral Sclerosis","volume":"19","author":"Tallon","year":"2022","journal-title":"Neurotherapeutics"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Neale, J.H., and Yamamoto, T. (2020). N-Acetylaspartylglutamate (NAAG) and Glutamate Carboxypeptidase II: An Abundant Peptide Neurotransmitter-Enzyme System with Multiple Clinical Applications. Prog. Neurobiol., 184.","DOI":"10.1016\/j.pneurobio.2019.101722"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"760270","DOI":"10.3389\/fnagi.2021.760270","article-title":"Glutamate Carboxypeptidase II in Aging Rat Prefrontal Cortex Impairs Working Memory Performance","volume":"13","author":"Datta","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1111\/jnc.13123","article-title":"Mice Lacking Glutamate Carboxypeptidase II Develop Normally, but Are Less Susceptible to Traumatic Brain Injury","volume":"134","author":"Gao","year":"2015","journal-title":"J. Neurochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3786","DOI":"10.1111\/cns.14299","article-title":"Deletion of Glutamate Carboxypeptidase II (GCPII), but Not GCPIII, Provided Long-term Benefits in Mice with Traumatic Brain Injury","volume":"29","author":"Ji","year":"2023","journal-title":"CNS Neurosci. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.jns.2006.05.052","article-title":"The Preventive and Therapeutic Effects of GCPII (NAALADase) Inhibition on Painful and Sensory Diabetic Neuropathy","volume":"247","author":"Zhang","year":"2006","journal-title":"J. Neurol. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1007\/s12640-009-9114-1","article-title":"Glutamate Carboxypeptidase Inhibition Reduces the Severity of Chemotherapy-Induced Peripheral Neurotoxicity in Rat","volume":"17","author":"Carozzi","year":"2010","journal-title":"Neurotox. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.brainres.2016.01.035","article-title":"Dose-Dependent Inhibition of GCPII to Prevent and Treat Cognitive Impairment in the EAE Model of Multiple Sclerosis","volume":"1635","author":"Hollinger","year":"2016","journal-title":"Brain Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1038\/s41536-022-00205-y","article-title":"Mature but Not Developing Schwann Cells Promote Axon Regeneration after Peripheral Nerve Injury","volume":"7","author":"Endo","year":"2022","journal-title":"NPJ Regen. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"608442","DOI":"10.3389\/fnmol.2020.608442","article-title":"Insights into the Role and Potential of Schwann Cells for Peripheral Nerve Repair From Studies of Development and Injury","volume":"13","author":"Balakrishnan","year":"2021","journal-title":"Front. Mol. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"553","DOI":"10.5966\/sctm.2013-0011","article-title":"Plastic Fantastic: Schwann Cells and Repair of the Peripheral Nervous System","volume":"2","author":"Kim","year":"2013","journal-title":"Stem Cells Transl. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"9086","DOI":"10.1523\/JNEUROSCI.1453-17.2017","article-title":"After Nerve Injury, Lineage Tracing Shows That Myelin and Remak Schwann Cells Elongate Extensively and Branch to Form Repair Schwann Cells, Which Shorten Radically on Remyelination","volume":"37","author":"Pilch","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.neuron.2012.06.021","article-title":"C-Jun Reprograms Schwann Cells of Injured Nerves to Generate a Repair Cell Essential for Regeneration","volume":"75","author":"Latouche","year":"2012","journal-title":"Neuron"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1083\/jcb.201503019","article-title":"Schwann Cell Autophagy, Myelinophagy, Initiates Myelin Clearance from Injured Nerves","volume":"210","author":"Carty","year":"2015","journal-title":"J. Cell Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/j.cell.2015.07.021","article-title":"Macrophage-Induced Blood Vessels Guide Schwann Cell-Mediated Regeneration of Peripheral Nerves","volume":"162","author":"Cattin","year":"2015","journal-title":"Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3438","DOI":"10.1111\/febs.13816","article-title":"Blocking Glutamate Carboxypeptidase II Inhibits Glutamate Excitotoxicity and Regulates Immune Responses in Experimental Autoimmune Encephalomyelitis","volume":"283","author":"Ha","year":"2016","journal-title":"FEBS J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neurobiolaging.2016.05.004","article-title":"An Attenuated Immune Response by Schwann Cells and Macrophages Inhibits Nerve Regeneration in Aged Rats","volume":"45","author":"Scheib","year":"2016","journal-title":"Neurobiol. Aging"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"33","DOI":"10.3389\/fncel.2019.00033","article-title":"The Success and Failure of the Schwann Cell Response to Nerve Injury","volume":"13","author":"Jessen","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1523\/JNEUROSCI.3591-09.2010","article-title":"Proteasomal Degradation of Glutamine Synthetase Regulates Schwann Cell Differentiation","volume":"30","author":"Saitoh","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Fu, Y., Sun, W., Shi, Y., Shi, R., and Cheng, J.-X. (2009). Glutamate Excitotoxicity Inflicts Paranodal Myelin Splitting and Retraction. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0006705"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5744","DOI":"10.1523\/JNEUROSCI.6810-10.2011","article-title":"Reduced BACE1 Activity Enhances Clearance of Myelin Debris and Regeneration of Axons in the Injured Peripheral Nervous System","volume":"31","author":"Farah","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/S0003-2697(02)00286-5","article-title":"Kinetics and Inhibition of Glutamate Carboxypeptidase II Using a Microplate Assay","volume":"310","author":"Rojas","year":"2002","journal-title":"Anal. Biochem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.freeradbiomed.2021.01.047","article-title":"Transgenic Expression of SOD1 Specifically in Neurons of Sod1 Deficient Mice Prevents Defects in Muscle Mitochondrial Function and Calcium Handling","volume":"165","author":"Su","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Huang, M., Tallon, C., Zhu, X., Huizar, K.D.J., Picciolini, S., Thomas, A.G., Tenora, L., Liyanage, W., Rod\u00e0, F., and Gualerzi, A. (2023). Microglial-Targeted nSMase2 Inhibitor Fails to Reduce Tau Propagation in PS19 Mice. Pharmaceutics, 15.","DOI":"10.20944\/preprints202308.1071.v1"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Su, Y., Claflin, D.R., Huang, M., Davis, C.S., Macpherson, P.C.D., Richardson, A., Van Remmen, H., and Brooks, S.V. (2021). Deletion of Neuronal CuZnSOD Accelerates Age-Associated Muscle Mitochondria and Calcium Handling Dysfunction That Is Independent of Denervation and Precedes Sarcopenia. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910735"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Numata-Uematasu, Y., Wakatsuki, S., Kobayashi-Ujiie, Y., Sakai, K., Ichinohe, N., and Araki, T. (2023). In Vitro Myelination Using Explant Culture of Dorsal Root Ganglia: An Efficient Tool for Analyzing Peripheral Nerve Differentiation and Disease Modeling. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0285897"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/978-1-4939-7862-5_9","article-title":"DRG Neuron\/Schwann Cells Myelinating Cocultures","volume":"Volume 1791","author":"Woodhoo","year":"2018","journal-title":"Myelin"},{"key":"ref_59","first-page":"1733","article-title":"Novel Neuron-Schwann Cell Co-Culture Models to Study Peripheral Nerve Degeneration and Regeneration","volume":"18","author":"Sango","year":"2023","journal-title":"Neural Regen. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1007\/BF01187086","article-title":"Wallerian Degeneration in the Peripheral Nervous System: Participation of Both Schwann Cells and Macrophages in Myelin Degradation","volume":"18","author":"Stoll","year":"1989","journal-title":"J. Neurocytol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/13\/6893\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:03:16Z","timestamp":1760108596000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/13\/6893"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,23]]},"references-count":60,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["ijms25136893"],"URL":"https:\/\/doi.org\/10.3390\/ijms25136893","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,23]]}}}