{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:18Z","timestamp":1787028558762,"version":"build-2736575974"},"reference-count":73,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T00:00:00Z","timestamp":1743292800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Repulsive guidance molecule-a (RGMa) has emerged as a significant therapeutic target in a variety of neurological disorders, including neurodegenerative diseases and acute conditions. This review comprehensively examines the multifaceted role of RGMa in central nervous system (CNS) pathologies such as Alzheimer\u2019s disease, Parkinson\u2019s disease, amyotrophic lateral sclerosis, multiple sclerosis, neuromyelitis optica spectrum disorder, spinal cord injury, stroke, vascular dementia, auditory neuropathy, and epilepsy. The mechanisms through which RGMa contributes to neuroinflammation, neuronal degeneration, and impaired axonal regeneration are herein discussed. Evidence from preclinical studies associate RGMa overexpression with negative outcomes, such as increased neuroinflammation and synaptic loss, while RGMa inhibition, particularly the use of agents like elezanumab, has shown promise in enhancing neuronal survival and functional recovery. RGMa\u2019s responses concerning immunomodulation and neurogenesis highlight its potential as a therapeutic avenue. We emphasize RGMa\u2019s critical role in CNS pathology and its potential to pave the way for innovative treatment strategies in neurological disorders. While preclinical findings are encouraging so far, further clinical trials are needed to validate the safety and efficacy of RGMa-targeted therapies.<\/jats:p>","DOI":"10.3390\/ijms26073221","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T03:25:02Z","timestamp":1743391502000},"page":"3221","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Repulsive Guidance Molecule-A as a Therapeutic Target Across Neurological Disorders: An Update"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5651-7082","authenticated-orcid":false,"given":"Vasilis-Spyridon","family":"Tseriotis","sequence":"first","affiliation":[{"name":"Department of Neurology, Agios Pavlos General Hospital of Thessaloniki, 55134 Thessaloniki, Greece"},{"name":"Laboratory of Clinical Pharmacology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9572-2369","authenticated-orcid":false,"given":"Andreas","family":"Liampas","sequence":"additional","affiliation":[{"name":"Department of Neurology, Nicosia General Hospital, Strovolos, 2031 Nicosia, Cyprus"},{"name":"Department of Neurology, Medical School, University of Cyprus, 1678 Nicosia, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4385-851X","authenticated-orcid":false,"given":"Irene Zacharo","family":"Lazaridou","sequence":"additional","affiliation":[{"name":"Department of Neurology, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6309-8410","authenticated-orcid":false,"given":"Sofia","family":"Karachrysafi","sequence":"additional","affiliation":[{"name":"Research Team \u201cHistologistas\u201d, Interinstitutional Postgraduate Program \u201cHealth and Environmental Factors\u201d, Department of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"},{"name":"Laboratory of Histology-Embryology, Department of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George D.","family":"Vavougios","sequence":"additional","affiliation":[{"name":"Department of Neurology, Nicosia General Hospital, Strovolos, 2031 Nicosia, Cyprus"},{"name":"Department of Neurology, Medical School, University of Cyprus, 1678 Nicosia, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5386-4273","authenticated-orcid":false,"given":"Georgios M.","family":"Hadjigeorgiou","sequence":"additional","affiliation":[{"name":"Department of Neurology, Nicosia General Hospital, Strovolos, 2031 Nicosia, Cyprus"},{"name":"Department of Neurology, Medical School, University of Cyprus, 1678 Nicosia, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0709-5407","authenticated-orcid":false,"given":"Theodora","family":"Papamitsou","sequence":"additional","affiliation":[{"name":"Research Team \u201cHistologistas\u201d, Interinstitutional Postgraduate Program \u201cHealth and Environmental Factors\u201d, Department of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"},{"name":"Laboratory of Histology-Embryology, Department of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios","family":"Kouvelas","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianthi","family":"Arnaoutoglou","sequence":"additional","affiliation":[{"name":"First Department of Neurology, AHEPA General Hospital of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3781-9680","authenticated-orcid":false,"given":"Chryssa","family":"Pourzitaki","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5952-5106","authenticated-orcid":false,"given":"Theodoros","family":"Mavridis","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tallaght University Hospital (TUH)\/The Adelaide and Meath Hospital, Incorporating the National Children\u2019s Hospital (AMNCH), D24 NR0A Dublin, Ireland"},{"name":"1st Neurology Department, Eginition Hospital, Medical School, National & Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zhang, L., Tang, S., Ma, Y., Liu, J., Monnier, P., Li, H., Zhang, R., Yu, G., Zhang, M., and Li, Y. 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