{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:43:30Z","timestamp":1760060610632,"version":"build-2065373602"},"reference-count":138,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish Ministry of Science, Innovation and Universities","award":["PDI-2021-1232690B-I00"],"award-info":[{"award-number":["PDI-2021-1232690B-I00"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Demyelinating diseases, such as multiple sclerosis, involve oligodendrocyte death, myelin loss, and neuronal death. These processes have been extensively studied, and a causal relationship has been demonstrated between them: destruction of oligodendrocytes results in myelin deficiency, which subsequently leads to neurodegeneration and the consequent loss of sensory, motor, and cognitive functions. Currently, myelinopathies lack fully effective treatments. Available drugs primarily focus on controlling the immune response without directly promoting myelin regeneration or restoring neuronal functionality. Alongside these treatments, pharmaceutical research has increasingly focused on developing therapies that stimulate oligodendroglial lineage differentiation and myelin sheath regeneration. Despite these advances, the lack of suitable preclinical models has been a significant obstacle in evaluating new therapeutic compounds. In this review, we present the main animal models used in the preclinical phase for the study of myelin-related diseases and their role in the development of new therapies. In addition, we highlight the usefulness of R-Ras animal models for assessing the efficacy of compounds that promote oligodendrocyte differentiation.<\/jats:p>","DOI":"10.3390\/biom15091309","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T14:23:50Z","timestamp":1757600630000},"page":"1309","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Animal Models for Multiple Sclerosis: R-Ras GTPases in Myelin Pathophysiology"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2010-1549","authenticated-orcid":false,"given":"Gema M.","family":"Esteban-Ortega","sequence":"first","affiliation":[{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa (CBM), Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"},{"name":"Instituto Universitario de Biolog\u00eda Molecular, Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2179-2521","authenticated-orcid":false,"given":"Gonzalo","family":"Garcia-Martin","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa (CBM), Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2280-8233","authenticated-orcid":false,"given":"Beatriz","family":"Cubelos","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa (CBM), Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"},{"name":"Instituto Universitario de Biolog\u00eda Molecular, Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/nature11007","article-title":"Glycolytic Oligodendrocytes Maintain Myelin and Long-Term Axonal Integrity","volume":"485","author":"Funfschilling","year":"2012","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/nature11314","article-title":"Oligodendroglia Metabolically Support Axons and Contribute to Neurodegeneration","volume":"487","author":"Lee","year":"2012","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/s41593-023-01558-3","article-title":"Oligodendrocyte\u2013Axon Metabolic Coupling Is Mediated by Extracellular K+ and Maintains Axonal Health","volume":"27","author":"Looser","year":"2024","journal-title":"Nat. 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