{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:21:44Z","timestamp":1792178504100,"version":"4.4.0"},"reference-count":148,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Monoclonal antibodies (mAbs) have revolutionized the treatment landscape for neurological diseases, providing targeted, mechanism-based therapies for conditions ranging from autoimmune demyelinating disorders to neurodegenerative diseases. In multiple sclerosis (MS), mAbs against CD20, CD52, and \u03b14-integrins offer disease-modifying efficacy by altering immune responses, depleting B cells, or blocking leukocyte migration into the central nervous system (CNS). Similarly, novel agents under investigation, such as frexalimab and foralumab, modulate T and B cell interactions and regulatory immunity. In neuromyelitis optica spectrum disorder (NMOSD), mAbs targeting IL-6, the complement cascade, and B cell lineage have demonstrated significant clinical benefit in preventing relapses and disability. In Alzheimer\u2019s disease (AD), several anti-amyloid mAbs have gained regulatory approval. Anti-tau and anti-\u03b1-synuclein antibodies, though promising, have shown limited efficacy to date in AD and parkinson\u2019s disease (PD), respectively. The evolving armamentarium of mAbs reflects a paradigm shift toward personalized neuroimmunology and neurodegeneration-targeted treatments, based on ongoing clarification of molecular and neuroinflammatory mechanisms. In this context, the present review summarizes current evidence on mAbs used in CNS disorders, with an emphasis on their pathophysiological targets, molecular mechanisms, clinical efficacy, and safety.<\/jats:p>","DOI":"10.3390\/ijms26199398","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T08:31:28Z","timestamp":1758875488000},"page":"9398","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Monoclonal Antibodies as Therapeutic Agents in Autoimmune and Neurodegenerative Diseases of the Central Nervous System: Current Evidence on Molecular Mechanisms and Future Directions"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1781-2799","authenticated-orcid":false,"given":"Charalampos","family":"Skarlis","sequence":"first","affiliation":[{"name":"Research Immunogenetics Laboratory, First Department of Neurology, School of Medicine, National and Kapodistrian University of Athens, NKUA, Aeginition University Hospital, Vas. Sofias 72-74, 11528 Athens, Greece"},{"name":"Multiple Sclerosis and Demyelinating Diseases Unit, Center of Expertise for Rare Demyelinating and Autoinflammatory Diseases of CNS, First Department of Neurology, School of Medicine, National and Kapodistrian University of Athens, NKUA, Aeginition University Hospital, Vas. Sofias 72-74, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1426-3384","authenticated-orcid":false,"given":"Efthalia","family":"Angelopoulou","sequence":"additional","affiliation":[{"name":"Neurodegenerative Diseases and Rare Dementias Unit, First Department of Neurology, School of Medicine, National and Kapodistrian University of Athens, NKUA, Aeginition University Hospital, Vas. 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