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AD006.289\u2014NEWDEM"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neurodegenerative diseases (NDs), including Alzheimer\u2019s disease, Parkinson\u2019s disease, amyotrophic lateral sclerosis\/motor neuron disease, and multiple sclerosis, are characterized by progressive loss of neuronal structure and function, leading to severe cognitive, motor, and behavioral impairments. They pose a significant and growing challenge due to their rising prevalence and impact on global health systems. The societal and emotional toll on patients, caregivers, and healthcare infrastructures is considerable. While significant progress has been made in elucidating the pathological hallmarks of these disorders, the underlying cellular and molecular mechanisms remain incompletely understood. Increasing evidence implicates oligodendrocytes and their progenitors\u2014oligodendrocyte progenitor cells (OPCs)\u2014in the pathogenesis of several NDs, beyond their traditionally recognized role in demyelinating conditions such as MS. Oligodendrocytes are essential for axonal myelination, metabolic support, and neural circuit modulation in the central nervous system. Disruptions in oligodendrocyte function and myelin integrity\u2014manifesting as demyelination, hypomyelination, or dysmyelination\u2014have been associated with disease progression in various neurodegenerative contexts. This review consolidates recent findings on the role of OPCs in NDs, explores the concept of myelin plasticity, and discusses therapeutic strategies targeting oligodendrocyte dysfunction. By highlighting emerging research in oligodendrocyte biology, this review aims to provide a short overview of its relevance to neurodegenerative disease progression and potential therapeutic advances.<\/jats:p>","DOI":"10.3390\/ijms26104623","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T10:58:07Z","timestamp":1747047487000},"page":"4623","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The Role of Oligodendrocytes in Neurodegenerative Diseases: Unwrapping the Layers"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-8331-3666","authenticated-orcid":false,"given":"Leona","family":"Bokulic Panichi","sequence":"first","affiliation":[{"name":"Neuroscience Department, Azienda Ospedaliero-Universitaria Pisana, 56126 Pisa, Italy"},{"name":"NeuroCare Onlus, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9692-7347","authenticated-orcid":false,"given":"Stefano","family":"Stanca","sequence":"additional","affiliation":[{"name":"NeuroCare Onlus, 56124 Pisa, Italy"},{"name":"Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Dolciotti","sequence":"additional","affiliation":[{"name":"Neuroscience Department, Azienda Ospedaliero-Universitaria Pisana, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0767-1558","authenticated-orcid":false,"given":"Paolo","family":"Bongioanni","sequence":"additional","affiliation":[{"name":"Neuroscience Department, Azienda Ospedaliero-Universitaria Pisana, 56126 Pisa, Italy"},{"name":"NeuroCare Onlus, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,12]]},"reference":[{"key":"ref_1","unstructured":"GBD 2016 Dementia Collaborators (2019). 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