{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T23:38:07Z","timestamp":1783035487559,"version":"3.54.6"},"reference-count":119,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T00:00:00Z","timestamp":1737417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000738","name":"Veterans Affairs Biomedical Laboratory Research and Development Service","doi-asserted-by":"publisher","award":["I01 BX005193"],"award-info":[{"award-number":["I01 BX005193"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"Veterans Affairs Biomedical Laboratory Research and Development Service","doi-asserted-by":"publisher","award":["R01EY028569"],"award-info":[{"award-number":["R01EY028569"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"Veterans Affairs Biomedical Laboratory Research and Development Service","doi-asserted-by":"publisher","award":["P30EY031631"],"award-info":[{"award-number":["P30EY031631"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["I01 BX005193"],"award-info":[{"award-number":["I01 BX005193"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01EY028569"],"award-info":[{"award-number":["R01EY028569"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["P30EY031631"],"award-info":[{"award-number":["P30EY031631"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Georgia intramural funds","award":["I01 BX005193"],"award-info":[{"award-number":["I01 BX005193"]}]},{"name":"University of Georgia intramural funds","award":["R01EY028569"],"award-info":[{"award-number":["R01EY028569"]}]},{"name":"University of Georgia intramural funds","award":["P30EY031631"],"award-info":[{"award-number":["P30EY031631"]}]},{"name":"Charlie Norwood VA Medical Center, Augusta, GA, USA","award":["I01 BX005193"],"award-info":[{"award-number":["I01 BX005193"]}]},{"name":"Charlie Norwood VA Medical Center, Augusta, GA, USA","award":["R01EY028569"],"award-info":[{"award-number":["R01EY028569"]}]},{"name":"Charlie Norwood VA Medical Center, Augusta, GA, USA","award":["P30EY031631"],"award-info":[{"award-number":["P30EY031631"]}]},{"name":"NIH\/NEI to the Augusta University Vision Discovery Institute","award":["I01 BX005193"],"award-info":[{"award-number":["I01 BX005193"]}]},{"name":"NIH\/NEI to the Augusta University Vision Discovery Institute","award":["R01EY028569"],"award-info":[{"award-number":["R01EY028569"]}]},{"name":"NIH\/NEI to the Augusta University Vision Discovery Institute","award":["P30EY031631"],"award-info":[{"award-number":["P30EY031631"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Multiple sclerosis (MS) is a highly disabling chronic neurological condition affecting young adults. Inflammation, demyelination, and axonal damage are key pathological features of MS and its animal model, experimental autoimmune encephalomyelitis (EAE). Our previous work demonstrated that inhibiting spermine oxidase (SMOX) with MDL72527, a selective irreversible pharmacological inhibitor, significantly reduced clinical symptoms, retinal ganglion cell (RGC) loss, and optic nerve inflammation in EAE mice. The present study explored the broader therapeutic potential of SMOX inhibition, focusing on myelin preservation, axonal integrity, and visual function in the EAE model. Electron microscopy of optic nerve cross-sections showed significant preservation of myelin thickness and axonal integrity due to SMOX inhibition. The quantitative assessment showed that g-ratio and axon count metrics were significantly improved in MDL72527-treated EAE mice compared to their vehicle-treated counterparts. Immunofluorescence studies confirmed these findings, showing increased preservation of myelin and axonal proteins in MDL72527-treated EAE mice compared to the vehicle-treated group. Functional assessment studies (Electroretinography) demonstrated significant improvement in RGC function and axonal conduction in EAE mice treated with MDL72527. Furthermore, SMOX inhibition downregulated the expression of galectin3 (Gal3), a mediator of neuroinflammation, indicating Gal3\u2019s role in SMOX-mediated neuroprotection. This study provides compelling evidence for the potential of SMOX inhibition as a therapeutic strategy in multiple sclerosis and other demyelinating disorders.<\/jats:p>","DOI":"10.3390\/biom15020158","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T05:47:42Z","timestamp":1737438462000},"page":"158","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Targeting SMOX Preserves Optic Nerve Myelin, Axonal Integrity, and Visual Function in Multiple Sclerosis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3196-8520","authenticated-orcid":false,"given":"Harry O.","family":"Henry-Ojo","sequence":"first","affiliation":[{"name":"Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30907, USA"},{"name":"Research Division, Charlie Norwood VA Medical Center, Augusta, GA 30901, USA"},{"name":"Culver Vision Discovery Institute, Augusta University, Augusta, GA 30907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5129-5318","authenticated-orcid":false,"given":"Fang","family":"Liu","sequence":"additional","affiliation":[{"name":"Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30907, USA"},{"name":"Research Division, Charlie Norwood VA Medical Center, Augusta, GA 30901, USA"},{"name":"Culver Vision Discovery Institute, Augusta University, Augusta, GA 30907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8842-622X","authenticated-orcid":false,"given":"S. Priya","family":"Narayanan","sequence":"additional","affiliation":[{"name":"Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30907, USA"},{"name":"Research Division, Charlie Norwood VA Medical Center, Augusta, GA 30901, USA"},{"name":"Culver Vision Discovery Institute, Augusta University, Augusta, GA 30907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Qian, Z., Li, Y., Guan, Z., Guo, P., Zheng, K., Du, Y., Yin, S., Chen, B., Wang, H., and Jiang, J. (2023). Global, regional, and national burden of multiple sclerosis from 1990 to 2019: Findings of global burden of disease study 2019. Front. Public Health, 11.","DOI":"10.3389\/fpubh.2023.1073278"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"a028936","DOI":"10.1101\/cshperspect.a028936","article-title":"Multiple Sclerosis Pathology","volume":"8","author":"Lassmann","year":"2018","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/S1474-4422(10)70064-8","article-title":"The changing demographic pattern of multiple sclerosis epidemiology","volume":"9","author":"Sorensen","year":"2010","journal-title":"Lancet Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"515","DOI":"10.3174\/ajnr.A2340","article-title":"Identification and clinical impact of multiple sclerosis cortical lesions as assessed by routine 3T MR imaging","volume":"32","author":"Mike","year":"2011","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/B978-0-444-52001-2.00011-X","article-title":"Multiple sclerosis: Diagnosis, differential diagnosis, and clinical presentation","volume":"Volume 122","author":"Gelfand","year":"2014","journal-title":"Handbook of Clinical Neurology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/S1474-4422(20)30277-5","article-title":"Cognitive impairment in multiple sclerosis: Clinical management, MRI, and therapeutic avenues","volume":"19","author":"Benedict","year":"2020","journal-title":"Lancet Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1177\/1352458508096684","article-title":"Cognitive impairment in multiple sclerosis","volume":"15","author":"Patti","year":"2009","journal-title":"Mult. Scler."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s13148-019-0632-2","article-title":"The emerging role of epigenetics in human autoimmune disorders","volume":"11","author":"Mazzone","year":"2019","journal-title":"Clin. Epigenet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e700","DOI":"10.1212\/NXI.0000000000000700","article-title":"Chronic demyelination exacerbates neuroaxonal loss in patients with MS with unilateral optic neuritis","volume":"7","author":"You","year":"2020","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1093\/cei\/uxac063","article-title":"Immunopathology of the optic nerve in multiple sclerosis","volume":"209","author":"Marzin","year":"2022","journal-title":"Clin. Exp. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1002\/ana.20851","article-title":"Quantifying axonal loss after optic neuritis with optical coherence tomography","volume":"59","author":"Costello","year":"2006","journal-title":"Ann. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"195","DOI":"10.2147\/EB.S54131","article-title":"Optic neuritis as an early sign of multiple sclerosis","volume":"8","author":"Kale","year":"2016","journal-title":"Eye Brain"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Optic Neuritis Study Group (2008). Multiple sclerosis risk after optic neuritis: Final optic neuritis treatment trial follow-up. Arch. Neurol., 65, 727\u2013732.","DOI":"10.1001\/archneur.65.6.727"},{"key":"ref_14","first-page":"616","article-title":"The Diagnosis and Treatment of Optic Neuritis","volume":"112","author":"Wilhelm","year":"2015","journal-title":"Dtsch. Arztebl. Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S1474-4422(22)00187-9","article-title":"Optic neuritis and autoimmune optic neuropathies: Advances in diagnosis and treatment","volume":"22","author":"Bennett","year":"2023","journal-title":"Lancet Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5113","DOI":"10.1007\/s00415-023-11920-x","article-title":"An update on optic neuritis","volume":"270","author":"Kraker","year":"2023","journal-title":"J. Neurol."},{"key":"ref_17","first-page":"10","article-title":"Optic neuritis: Current challenges in diagnosis and management","volume":"36","author":"Costello","year":"2023","journal-title":"Curr. Opin. Neurol."},{"key":"ref_18","first-page":"1236","article-title":"Optic Neuritis","volume":"25","author":"Bennett","year":"2019","journal-title":"Continuum"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.exer.2009.02.009","article-title":"Retinal pathway origins of the pattern ERG of the mouse","volume":"89","author":"Miura","year":"2009","journal-title":"Exp. Eye Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1038\/nprot.2006.285","article-title":"Active induction of experimental allergic encephalomyelitis","volume":"1","author":"Stromnes","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"137","DOI":"10.3109\/08916939309043888","article-title":"T helper 1 (Th1) functional phenotype of human myelin basic protein-specific T lymphocytes","volume":"15","author":"Voskuhl","year":"1993","journal-title":"Autoimmunity"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/S1357-4310(99)01639-1","article-title":"Animal models for autoimmune demyelinating disorders of the nervous system","volume":"6","author":"Gold","year":"2000","journal-title":"Mol. Med. Today"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1177\/1352458518805246","article-title":"Animal models of multiple sclerosis: From rodents to zebrafish","volume":"25","author":"Burrows","year":"2019","journal-title":"Mult. Scler."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Inoue, K., Tsutsui, H., Akatsu, H., Hashizume, Y., Matsukawa, N., Yamamoto, T., and Toyo\u2019oka, T. (2013). Metabolic profiling of Alzheimer\u2019s disease brains. Sci. Rep., 3.","DOI":"10.1038\/srep02364"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"176823","DOI":"10.1016\/j.ejphar.2024.176823","article-title":"Spermidine as an epigenetic regulator of autophagy in neurodegenerative disorders","volume":"979","author":"Satarker","year":"2024","journal-title":"Eur. J. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Peng, K.W., Klotz, A., Guven, A., Kapadnis, U., Ravipaty, S., Tolstikov, V., Vemulapalli, V., Rodrigues, L.O., Li, H., and Kellogg, M.D. (2024). Identification and validation of N-acetylputrescine in combination with non-canonical clinical features as a Parkinson\u2019s disease biomarker panel. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-60872-3"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1146\/annurev-biochem-071322-021330","article-title":"Polyamines in Parkinson\u2019s Disease: Balancing Between Neurotoxicity and Neuroprotection","volume":"92","author":"Vrijsen","year":"2023","journal-title":"Annu. Rev. Biochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1002\/ana.25516","article-title":"A metabolic profile of polyamines in parkinson disease: A promising biomarker","volume":"86","author":"Saiki","year":"2019","journal-title":"Ann. Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1007\/s10571-019-00783-4","article-title":"Spermidine Exhibits Protective Effects Against Traumatic Brain Injury","volume":"40","author":"Huang","year":"2020","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1089\/neu.2009.1097","article-title":"Polyamine catabolism is enhanced after traumatic brain injury","volume":"27","author":"Zahedi","year":"2010","journal-title":"J. Neurotrauma"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e035837","DOI":"10.1161\/JAHA.124.035837","article-title":"Plasma Polyamines and Short-Term Adverse Outcomes Among Patients with Ischemic Stroke: A Prospective Cohort Study","volume":"13","author":"Yang","year":"2024","journal-title":"J. Am. Heart Assoc."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"113066","DOI":"10.1016\/j.expneurol.2019.113066","article-title":"Acrolein is involved in ischemic stroke-induced neurotoxicity through spermidine\/spermine-N1-acetyltransferase activation","volume":"323","author":"Liu","year":"2020","journal-title":"Exp. Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1017\/S0317167100006247","article-title":"The role of polyamine metabolism in neuronal injury following cerebral ischemia","volume":"36","author":"Kim","year":"2009","journal-title":"Can. J. Neurol. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"eabc4275","DOI":"10.1126\/sciadv.abc4275","article-title":"De novo synthesis and salvage pathway coordinately regulate polyamine homeostasis and determine T cell proliferation and function","volume":"6","author":"Wu","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4186","DOI":"10.1016\/j.cell.2021.06.007","article-title":"Polyamine metabolism is a central determinant of helper T cell lineage fidelity","volume":"184","author":"Puleston","year":"2021","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s00726-011-1014-z","article-title":"Spermine oxidase: Ten years after","volume":"42","author":"Cervelli","year":"2012","journal-title":"Amino Acids"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Liu, F., Saul, A.B., Pichavaram, P., Xu, Z., Rudraraju, M., Somanath, P.R., Smith, S.B., Caldwell, R.B., and Narayanan, S.P. (2020). Pharmacological Inhibition of Spermine Oxidase Reduces Neurodegeneration and Improves Retinal Function in Diabetic Mice. J. Clin. Med., 9.","DOI":"10.3390\/jcm9020340"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1186\/s12974-020-01955-6","article-title":"Ablation of polyamine catabolic enzymes provokes Purkinje cell damage, neuroinflammation, and severe ataxia","volume":"17","author":"Zahedi","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1093\/toxsci\/kfy300","article-title":"Targeting Smox Is Neuroprotective and Ameliorates Brain Inflammation in Cerebral Ischemia\/Reperfusion Rats","volume":"168","author":"Fan","year":"2019","journal-title":"Toxicol. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.neuroscience.2010.11.018","article-title":"Anti-acrolein treatment improves behavioral outcome and alleviates myelin damage in experimental autoimmune encephalomyelitis mouse","volume":"173","author":"Leung","year":"2011","journal-title":"Neuroscience"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Tully, M., Tang, J., Zheng, L., Acosta, G., Tian, R., Hayward, L., Race, N., Mattson, D., and Shi, R. (2018). Systemic Acrolein Elevations in Mice with Experimental Autoimmune Encephalomyelitis and Patients with Multiple Sclerosis. Front. Neurol., 9.","DOI":"10.3389\/fneur.2018.00420"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Liu, F., Alfarhan, M., Baker, L., Shenoy, N., Liao, Y., Henry-Ojo, H.O., Somanath, P.R., and Narayanan, S.P. (2022). Treatment with MDL72527 Ameliorated Clinical Symptoms, Retinal Ganglion Cell Loss, Optic Nerve Inflammation, and Improved Visual Acuity in an Experimental Model of Multiple Sclerosis. Cells, 11.","DOI":"10.3390\/cells11244100"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Alfarhan, M., Liu, F., Shan, S., Pichavaram, P., Somanath, P.R., and Narayanan, S.P. (2022). Pharmacological Inhibition of Spermine Oxidase Suppresses Excitotoxicity Induced Neuroinflammation in Mouse Retina. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23042133"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1046\/j.1471-4159.1999.0720765.x","article-title":"Effects of MDL72527, a specific inhibitor of polyamine oxidase, on brain edema, ischemic injury volume, and tissue polyamine levels in rats after temporary middle cerebral artery occlusion","volume":"72","author":"Dogan","year":"1999","journal-title":"J. Neurochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1007\/s00726-013-1559-0","article-title":"Elevated ornithine decarboxylase activity promotes skin tumorigenesis by stimulating the recruitment of bulge stem cells but not via toxic polyamine catabolic metabolites","volume":"46","author":"Hayes","year":"2014","journal-title":"Amino Acids"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"8290","DOI":"10.1073\/pnas.140122097","article-title":"Activation of polyamine catabolism in transgenic rats induces acute pancreatitis","volume":"97","author":"Alhonen","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Diaz, E., Adhikary, S., Tepper, A., Riley, D., Ortiz-Meoz, R., Krosky, D., Buyck, C., Lamenca, C.M., Llaveria, J., and Fang, L. (2022). Structure of human spermine oxidase in complex with a highly selective allosteric inhibitor. Commun. Biol., 5.","DOI":"10.1038\/s42003-022-03735-9"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"8589","DOI":"10.1007\/s12035-019-01691-w","article-title":"Deletion of Arginase 2 Ameliorates Retinal Neurodegeneration in a Mouse Model of Multiple Sclerosis","volume":"56","author":"Palani","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Candadai, A.A., Liu, F., Fouda, A.Y., Alfarhan, M., Palani, C.D., Xu, Z., Caldwell, R.B., and Narayanan, S.P. (2021). Deletion of arginase 2 attenuates neuroinflammation in an experimental model of optic neuritis. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0247901"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1167\/tvst.9.3.22","article-title":"QuPath Automated Analysis of Optic Nerve Degeneration in Brown Norway Rats","volume":"9","author":"Mysona","year":"2020","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2469","DOI":"10.1167\/iovs.14-13943","article-title":"Robust mouse pattern electroretinograms derived simultaneously from each eye using a common snout electrode","volume":"55","author":"Chou","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.exer.2015.05.008","article-title":"Electrophysiological assessment of retinal ganglion cell function","volume":"141","author":"Porciatti","year":"2015","journal-title":"Exp. Eye Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1097\/IJG.0000000000000648","article-title":"Head-down Posture in Glaucoma Suspects Induces Changes in IOP, Systemic Pressure, and PERG That Predict Future Loss of Optic Nerve Tissue","volume":"26","author":"Porciatti","year":"2017","journal-title":"J. Glaucoma"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"108397","DOI":"10.1016\/j.exer.2020.108397","article-title":"Optimal timing for activation of sigma 1 receptor in the Pde6b(rd10)\/J (rd10) mouse model of retinitis pigmentosa","volume":"202","author":"Wang","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1167\/iovs.61.3.5","article-title":"Comparison of Neuroprotective Effects of Monomethylfumarate to the Sigma 1 Receptor Ligand (+)-Pentazocine in a Murine Model of Retinitis Pigmentosa","volume":"61","author":"Xiao","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Stassart, R.M., Mobius, W., Nave, K.A., and Edgar, J.M. (2018). The Axon-Myelin Unit in Development and Degenerative Disease. Front. Neurosci., 12.","DOI":"10.3389\/fnins.2018.00467"},{"key":"ref_57","first-page":"2055217320963474","article-title":"Functional evolution of visual involvement in experimental autoimmune encephalomyelitis","volume":"6","author":"Marenna","year":"2020","journal-title":"Mult. Scler. J. Exp. Transl. Clin."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/jon.12945","article-title":"Diffusely abnormal white matter in multiple sclerosis","volume":"32","author":"Cairns","year":"2022","journal-title":"J. Neuroimaging"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1038\/s41593-023-01366-9","article-title":"Myelin insulation as a risk factor for axonal degeneration in autoimmune demyelinating disease","volume":"26","author":"Schaffner","year":"2023","journal-title":"Nat. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"6911","DOI":"10.1038\/s41467-023-42570-2","article-title":"Microglia-mediated demyelination protects against CD8(+) T cell-driven axon degeneration in mice carrying PLP defects","volume":"14","author":"Groh","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3984","DOI":"10.1167\/iovs.18-23885","article-title":"Ultrastructural Morphology of the Optic Nerve Head in Aged and Glaucomatous Mice","volume":"59","author":"Zhu","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.jsps.2022.11.013","article-title":"Cathepsin-B inhibitor CA-074 attenuates retinopathy and optic neuritis in experimental autoimmune encephalomyelitis induced in SJL\/J mice","volume":"31","author":"Nadeem","year":"2023","journal-title":"Saudi Pharm. J."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Alrashdi, B., Dawod, B., Tacke, S., Kuerten, S., Cote, P.D., and Marshall, J.S. (2021). Mice Heterozygous for the Sodium Channel Scn8a (Nav1.6) Have Reduced Inflammatory Responses During EAE and Following LPS Challenge. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.533423"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Jahn, O., Siems, S.B., Kusch, K., Hesse, D., Jung, R.B., Liepold, T., Uecker, M., Sun, T., and Werner, H.B. (2020). The CNS Myelin Proteome: Deep Profile and Persistence After Post-mortem Delay. Front. Cell. Neurosci., 14.","DOI":"10.3389\/fncel.2020.00239"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/S0301-0082(99)00049-0","article-title":"Myelin synthesis in the peripheral nervous system","volume":"61","author":"Garbay","year":"2000","journal-title":"Prog. Neurobiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.neuroimage.2016.02.040","article-title":"Mapping an index of the myelin g-ratio in infants using magnetic resonance imaging","volume":"132","author":"Dean","year":"2016","journal-title":"Neuroimage"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.neuroimage.2016.09.018","article-title":"g-Ratio weighted imaging of the human spinal cord in vivo","volume":"145","author":"Duval","year":"2017","journal-title":"Neuroimage"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1113\/jphysiol.1951.sp004655","article-title":"A theory of the effects of fibre size in medullated nerve","volume":"115","author":"Rushton","year":"1951","journal-title":"J. Physiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.neuroimage.2017.11.064","article-title":"Experimental studies of g-ratio MRI in ex vivo mouse brain","volume":"167","author":"West","year":"2018","journal-title":"Neuroimage"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.dib.2015.05.019","article-title":"Quantitative analysis of the myelin g-ratio from electron microscopy images of the macaque corpus callosum","volume":"4","author":"Stikov","year":"2015","journal-title":"Data Brief."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"9794","DOI":"10.1523\/JNEUROSCI.2116-06.2006","article-title":"Protecting axonal degeneration by increasing nicotinamide adenine dinucleotide levels in experimental autoimmune encephalomyelitis models","volume":"26","author":"Kaneko","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1002\/jnr.24767","article-title":"Axonal mitochondria adjust in size depending on g-ratio of surrounding myelin during homeostasis and advanced remyelination","volume":"99","author":"Ineichen","year":"2021","journal-title":"J. Neurosci. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1056\/NEJM199801293380502","article-title":"Axonal transection in the lesions of multiple sclerosis","volume":"338","author":"Trapp","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1093\/brain\/123.2.308","article-title":"Axonal changes in chronic demyelinated cervical spinal cord plaques","volume":"123","author":"Lovas","year":"2000","journal-title":"Brain"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/s40478-019-0767-6","article-title":"Glial pathology and retinal neurotoxicity in the anterior visual pathway in experimental autoimmune encephalomyelitis","volume":"7","author":"Jin","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1146\/annurev.neuro.30.051606.094313","article-title":"Multiple sclerosis: An immune or neurodegenerative disorder?","volume":"31","author":"Trapp","year":"2008","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1046\/j.1469-7580.1998.19320195.x","article-title":"A strong myelin thickness-axon size correlation emerges in developing nerves despite independent growth of both parameters","volume":"193","author":"Fraher","year":"1998","journal-title":"J. Anat."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.neurobiolaging.2016.09.016","article-title":"Characterizing axonal myelination within the healthy population: A tract-by-tract mapping of effects of age and gender on the fiber g-ratio","volume":"49","author":"Cercignani","year":"2017","journal-title":"Neurobiol. Aging"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.neuroimage.2015.05.023","article-title":"In vivo histology of the myelin g-ratio with magnetic resonance imaging","volume":"118","author":"Stikov","year":"2015","journal-title":"Neuroimage"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s10633-022-09896-6","article-title":"Pattern ERGs suggest a possible retinal contribution to the visual acuity loss in acute optic neuritis","volume":"145","author":"Kleerekooper","year":"2022","journal-title":"Doc. Ophthalmol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1167\/tvst.13.8.1","article-title":"Correlation of Visual System Biomarkers with Motor Deficits in Experimental Autoimmune Encephalomyelitis-Optic Neuritis","volume":"13","author":"Elwood","year":"2024","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1167\/tvst.9.8.16","article-title":"Systemic Mesenchymal Stem Cell Treatment Mitigates Structural and Functional Retinal Ganglion Cell Degeneration in a Mouse Model of Multiple Sclerosis","volume":"9","author":"Gramlich","year":"2020","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1186\/s12974-018-1208-3","article-title":"Laquinimod protects the optic nerve and retina in an experimental autoimmune encephalomyelitis model","volume":"15","author":"Wilmes","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s12974-022-02416-y","article-title":"B cell-dependent EAE induces visual deficits in the mouse with similarities to human autoimmune demyelinating diseases","volume":"19","author":"Joly","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"101490","DOI":"10.1016\/j.xcrm.2024.101490","article-title":"Synaptic injury in the inner plexiform layer of the retina is associated with progression in multiple sclerosis","volume":"5","author":"Cordano","year":"2024","journal-title":"Cell Rep. Med."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Tsukamoto, Y., and Omi, N. (2017). Classification of Mouse Retinal Bipolar Cells: Type-Specific Connectivity with Special Reference to Rod-Driven AII Amacrine Pathways. Front. Neuroanat., 11.","DOI":"10.3389\/fnana.2017.00092"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000328979","article-title":"Muller glial cells in retinal disease","volume":"227","author":"Bringmann","year":"2012","journal-title":"Ophthalmologica"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/S0042-6989(99)00203-5","article-title":"Contribution to the kinetics and amplitude of the electroretinogram b-wave by third-order retinal neurons in the rabbit retina","volume":"40","author":"Dong","year":"2000","journal-title":"Vis. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1084\/jem.20041257","article-title":"IL-23 drives a pathogenic T cell population that induces autoimmune inflammation","volume":"201","author":"Langrish","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1002\/ana.21800","article-title":"Multiple sclerosis: Distribution of inflammatory cells in newly forming lesions","volume":"66","author":"Henderson","year":"2009","journal-title":"Ann. Neurol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s00401-019-02013-z","article-title":"Galectin-3, a novel endogenous TREM2 ligand, detrimentally regulates inflammatory response in Alzheimer\u2019s disease","volume":"138","author":"Ruiz","year":"2019","journal-title":"Acta Neuropathol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.4103\/1673-5374.391181","article-title":"Emerging role of galectin 3 in neuroinflammation and neurodegeneration","volume":"19","author":"Lozinski","year":"2024","journal-title":"Neural Regen. Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"4725","DOI":"10.1523\/JNEUROSCI.2312-22.2023","article-title":"Elevated Galectin-3 Is Associated with Aging, Multiple Sclerosis, and Oxidized Phosphatidylcholine-Induced Neurodegeneration","volume":"43","author":"Xue","year":"2023","journal-title":"J. Neurosci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/j.cell.2017.05.018","article-title":"A Unique Microglia Type Associated with Restricting Development of Alzheimer\u2019s Disease","volume":"169","author":"Spinrad","year":"2017","journal-title":"Cell"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.immuni.2017.08.008","article-title":"The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Microglia in Neurodegenerative Diseases","volume":"47","author":"Krasemann","year":"2017","journal-title":"Immunity"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1097\/WCO.0000000000000812","article-title":"Galectins in the brain: Advances in neuroinflammation, neuroprotection and therapeutic opportunities","volume":"33","author":"Barake","year":"2020","journal-title":"Curr. Opin. Neurol."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Paganelli, A., Diomede, F., Marconi, G.D., Pizzicannella, J., Rajan, T.S., Trubiani, O., and Paganelli, R. (2023). Inhibition of LPS-Induced Inflammatory Response of Oral Mesenchymal Stem Cells in the Presence of Galectin-3. Biomedicines, 11.","DOI":"10.3390\/biomedicines11061519"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1053\/j.gastro.2021.11.005","article-title":"Protective Role of Spermidine in Colitis and Colon Carcinogenesis","volume":"162","author":"Gobert","year":"2022","journal-title":"Gastroenterology"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"4465","DOI":"10.1038\/s41388-020-1304-6","article-title":"Spermine oxidase mediates Helicobacter pylori-induced gastric inflammation, DNA damage, and carcinogenic signaling","volume":"39","author":"Sierra","year":"2020","journal-title":"Oncogene"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Gobert, A.P., Al-Greene, N.T., Singh, K., Coburn, L.A., Sierra, J.C., Verriere, T.G., Luis, P.B., Schneider, C., Asim, M., and Allaman, M.M. (2018). Distinct Immunomodulatory Effects of Spermine Oxidase in Colitis Induced by Epithelial Injury or Infection. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01242"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"111183","DOI":"10.1016\/j.intimp.2023.111183","article-title":"Knockdown of Smox protects the integrity of the blood-brain barrier through antioxidant effect and Nrf2 pathway activation in stroke","volume":"126","author":"Wang","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"7259","DOI":"10.1007\/s12035-017-0864-0","article-title":"Glutamate Excitotoxicity Linked to Spermine Oxidase Overexpression","volume":"55","author":"Pietropaoli","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"e824","DOI":"10.1002\/iid3.824","article-title":"CircSmox knockdown alleviates PC12 cell apoptosis and inflammation in spinal cord injury by miR-340-5p\/Smurf1 axis","volume":"11","author":"Han","year":"2023","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Fairley, L.H., Lejri, I., Grimm, A., and Eckert, A. (2023). Spermidine Rescues Bioenergetic and Mitophagy Deficits Induced by Disease-Associated Tau Protein. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065297"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s10522-020-09900-z","article-title":"Spermidine, a caloric restriction mimetic, provides neuroprotection against normal and D-galactose-induced oxidative stress and apoptosis through activation of autophagy in male rats during aging","volume":"22","author":"Singh","year":"2021","journal-title":"Biogerontology"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Maglione, M., Kochlamazashvili, G., Eisenberg, T., Racz, B., Michael, E., Toppe, D., Stumpf, A., Wirth, A., Zeug, A., and Muller, F.E. (2019). Spermidine protects from age-related synaptic alterations at hippocampal mossy fiber-CA3 synapses. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-56133-3"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1111\/fcp.12880","article-title":"Spermidine reduced neuropathic pain in chronic constriction injury-induced peripheral neuropathy in rats","volume":"37","author":"Shirooie","year":"2023","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"e1720","DOI":"10.1038\/cddis.2015.93","article-title":"Spermidine promotes retinal ganglion cell survival and optic nerve regeneration in adult mice following optic nerve injury","volume":"6","author":"Noro","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"117","DOI":"10.3164\/jcbn.10-73","article-title":"Mitochondrial disorders in NSAIDs-induced small bowel injury","volume":"48","author":"Watanabe","year":"2011","journal-title":"J. Clin. Biochem. Nutr."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"373","DOI":"10.2165\/0129784-200808060-00004","article-title":"Statin adverse effects: A review of the literature and evidence for a mitochondrial mechanism","volume":"8","author":"Golomb","year":"2008","journal-title":"Am. J. Cardiovasc. Drugs"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"3429","DOI":"10.1038\/onc.2014.273","article-title":"Increased Helicobacter pylori-associated gastric cancer risk in the Andean region of Colombia is mediated by spermine oxidase","volume":"34","author":"Chaturvedi","year":"2015","journal-title":"Oncogene"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"15354","DOI":"10.1073\/pnas.1010203108","article-title":"Polyamine catabolism contributes to enterotoxigenic Bacteroides fragilis-induced colon tumorigenesis","volume":"108","author":"Goodwin","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1042\/BST0350343","article-title":"MDL 72527 and spermine oxidation products induce a lysosomotropic effect and mitochondrial alterations in tumour cells","volume":"35","author":"Agostinelli","year":"2007","journal-title":"Biochem. Soc. Trans."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1177\/13524585211008760","article-title":"Current status of neuroprotective and neuroregenerative strategies in multiple sclerosis: A systematic review","volume":"28","author":"Allanach","year":"2022","journal-title":"Mult. Scler."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e126329","DOI":"10.1172\/jci.insight.126329","article-title":"Myelin repair stimulated by CNS-selective thyroid hormone action","volume":"4","author":"Hartley","year":"2019","journal-title":"JCI Insight"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s40478-016-0309-4","article-title":"Clobetasol promotes remyelination in a mouse model of neuromyelitis optica","volume":"4","author":"Yao","year":"2016","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2776","DOI":"10.1093\/brain\/awx154","article-title":"Cell-based therapeutic strategies for multiple sclerosis","volume":"140","author":"Scolding","year":"2017","journal-title":"Brain"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.jare.2013.04.005","article-title":"Current concept in neural regeneration research: NSCs isolation, characterization and transplantation in various neurodegenerative diseases and stroke: A review","volume":"5","author":"Vishwakarma","year":"2014","journal-title":"J. Adv. Res."},{"key":"ref_119","first-page":"2055217316641704","article-title":"Blocking LINGO-1 in vivo reduces degeneration and enhances regeneration of the optic nerve","volume":"2","author":"Gresle","year":"2016","journal-title":"Mult. Scler. J. Exp. Transl. Clin."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/2\/158\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:32:49Z","timestamp":1759919569000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/2\/158"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,21]]},"references-count":119,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["biom15020158"],"URL":"https:\/\/doi.org\/10.3390\/biom15020158","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,21]]}}}