{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:04:44Z","timestamp":1790802284567,"version":"4.1.0"},"reference-count":99,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"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>Multiple sclerosis (MS) is traditionally recognized as a chronic immune-mediated disorder of the central nervous system (CNS), but increasing evidence suggests that systemic metabolic alterations may also contribute to its pathophysiology. Lipid abnormalities in MS have recently attracted renewed research interest, with studies focusing both on dysregulation of lipid signaling pathways and on alterations in standard lipid profile components, including total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), and non-HDL cholesterol. Although disturbances in serum lipid profiles are consistently reported in patients with MS, their origin remains unresolved. Emerging data indicate that dyslipidemia may stem from aberrant cholesterol metabolism within the CNS, secondary to demyelination and myelin sheath destruction, leading to the release of lipid-rich debris and subsequent systemic metabolic imbalance. These lipid changes appear to correlate with blood\u2013brain barrier (BBB) dysfunction, suggesting a link between peripheral lipid metabolism and CNS inflammation. This review summarizes current knowledge on the mechanisms underlying dyslipidemia in MS, its potential impact on disease progression, and its relevance as a possible therapeutic or biomarker target in future translational studies.<\/jats:p>","DOI":"10.3390\/ijms27020812","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T09:03:10Z","timestamp":1768381390000},"page":"812","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Role of Lipid Alteration in Multiple Sclerosis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4490-5325","authenticated-orcid":false,"given":"Agnieszka","family":"Damiza-Detmer","sequence":"first","affiliation":[{"name":"Department of Neurology and Stroke, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4540-0932","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Pawe\u0142czyk","sequence":"additional","affiliation":[{"name":"Department of Neurology and Stroke, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1305-1494","authenticated-orcid":false,"given":"Andrzej","family":"G\u0142\u0105bi\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Neurology and Stroke, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1016\/S0140-6736(08)61620-7","article-title":"Multiple sclerosis","volume":"372","author":"Compston","year":"2008","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/S1474-4422(25)00270-4","article-title":"Diagnosis of multiple sclerosis: 2024 revisions of the McDonald criteria","volume":"24","author":"Montalban","year":"2025","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1186\/1742-2094-8-127","article-title":"Serum lipid profiles are associated with disability and MRI outcomes in multiple sclerosis","volume":"8","author":"Zivadinov","year":"2011","journal-title":"J. Neuroinflamm."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Podbielska, M., O\u2019Keeffe, J., and Pokryszko-Dragan, A. (2021). New Insights into Multiple Sclerosis Mechanisms: Lipids on the Track to Control Inflammation and Neurodegeneration. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147319"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/S1474-4422(22)00289-7","article-title":"Multiple sclerosis progression: Time for a new mechanism-driven framework","volume":"22","author":"Kuhlmann","year":"2023","journal-title":"Lancet Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Bar-Or, A., and Darlington, P.J. (2011). The immunology of multiple sclerosis. Multiple Sclerosis Therapeutics, Cambridge University Press. [4th ed.].","DOI":"10.1017\/CBO9781139023986.006"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1002\/jnr.24062","article-title":"Multiple sclerosis: Presence of serum antibodies to lipids and predominance of cholesterol recognition","volume":"95","author":"Jurewicz","year":"2017","journal-title":"J. Neurosci. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/nrneurol.2012.203","article-title":"B cells and antibodies in multiple sclerosis pathogenesis and therapy","volume":"8","author":"Krumbholz","year":"2012","journal-title":"Nat. Rev. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s00401-018-1815-1","article-title":"Functional morphology of the blood\u2013brain barrier in health and disease","volume":"135","author":"Liebner","year":"2018","journal-title":"Acta Neuropathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1016\/S0140-6736(18)30481-1","article-title":"Multiple sclerosis","volume":"391","author":"Thompson","year":"2018","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s12987-020-00230-3","article-title":"A blood\u2013brain barrier overview on structure, function, impairment, and biomarkers of integrity","volume":"17","author":"Kadry","year":"2020","journal-title":"Fluids Barriers CNS"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1002\/iub.2662","article-title":"Central nervous system cholesterol metabolism in health and disease","volume":"74","author":"Ho","year":"2022","journal-title":"IUBMB Life"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1146\/annurev-biochem-032620-104801","article-title":"Lipoproteins in the Central Nervous System: From Biology to Pathobiology","volume":"91","author":"Raulin","year":"2022","journal-title":"Annu. Rev. Biochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"895","DOI":"10.3892\/mmr.2012.758","article-title":"Role of liver X receptors in cholesterol efflux and inflammatory signaling","volume":"5","author":"Zhu","year":"2012","journal-title":"Mol. Med. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"103088","DOI":"10.1016\/j.autrev.2022.103088","article-title":"The role of cholesterol metabolism in multiple sclerosis: From molecular pathophysiology to radiological and clinical disease activity","volume":"21","author":"Lorincz","year":"2022","journal-title":"Autoimmun. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"105841","DOI":"10.1016\/j.msard.2024.105841","article-title":"Dyslipidemias in multiple sclerosis","volume":"91","author":"Wicks","year":"2024","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1177\/1352458514533162","article-title":"An adverse lipid profile is associated with disability and progression in disability, in people with MS","volume":"20","author":"Tettey","year":"2014","journal-title":"Mult. Scler. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1136\/jnnp-2012-304740","article-title":"Lipid profiles are associated with lesion formation over 24 months in interferon-\u03b2 treated patients following the first demyelinating event","volume":"84","author":"Zivadinov","year":"2013","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"104374","DOI":"10.1016\/j.msard.2022.104374","article-title":"Cholesterol pathway biomarkers are associated with neuropsychological measures in multiple sclerosis","volume":"69","author":"Siddiqui","year":"2023","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e1729","DOI":"10.1212\/WNL.0000000000207777","article-title":"Exploring the Role of Plasma Lipids and Statin Interventions on Multiple Sclerosis Risk and Severity: A Mendelian Randomization Study","volume":"101","author":"Almramhi","year":"2023","journal-title":"Neurology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.neulet.2018.10.030","article-title":"Cholesterol level correlate with disability score in patients with relapsing-remitting form of multiple sclerosis","volume":"687","year":"2018","journal-title":"Neurosci. Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"srep43410","DOI":"10.1038\/srep43410","article-title":"Relapsing-remitting multiple sclerosis patients display an altered lipoprotein profile with dysfunctional HDL","volume":"7","author":"Jorissen","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_23","first-page":"1083","article-title":"Cholesterol in myelin biogenesis and hypomyelinating disorders","volume":"1851","author":"Saher","year":"2015","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Cell Biol. Lipids"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e1002605","DOI":"10.1371\/journal.pbio.1002605","article-title":"Oligodendroglial myelination requires astrocyte-derived lipids","volume":"15","author":"Camargo","year":"2017","journal-title":"PLoS Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1021\/acschemneuro.5c00703","article-title":"Temporal dynamics of CNS cholesterol esters correlate with demyelination and remyelination","volume":"17","author":"Mohotti","year":"2025","journal-title":"ACS Chem. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1152\/physrev.00031.2018","article-title":"Myelin in the Central Nervous System: Structure, Function, and Pathology","volume":"99","author":"Stadelmann","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1016\/S0022-2275(20)31605-9","article-title":"Characterization of four lipoprotein classes in human cerebrospinal fluid","volume":"42","author":"Koch","year":"2001","journal-title":"J. Lipid Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"14352","DOI":"10.1016\/S0021-9258(18)47945-8","article-title":"Lipoproteins and their receptors in the central nervous system. Characterization of the lipoproteins in cerebrospinal fluid and identification of apolipoprotein B,E(LDL) receptors in the brain","volume":"262","author":"Boyles","year":"1987","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Rajha, H.E., Hassanein, A., Mesilhy, R., Nurulhaque, Z., Elghoul, N., Burgon, P.G., Al Saady, R.M., and Pedersen, S. (2025). Apolipoprotein A (ApoA) in Neurological Disorders: Connections and Insights. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26167908"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1124\/jpet.118.254201","article-title":"Apolipoprotein A-I Crosses the Blood-Brain Barrier through Clathrin-Independent and Cholesterol-Mediated Endocytosis","volume":"369","author":"Zhou","year":"2019","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1007\/s13238-014-0131-3","article-title":"Cholesterol metabolism and homeostasis in the brain","volume":"6","author":"Zhang","year":"2015","journal-title":"Protein Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S0304-3940(02)00887-X","article-title":"Changes in human plasma levels of the brain specific oxysterol 24S-hydroxycholesterol during progression of multiple sclerosis","volume":"331","author":"Leoni","year":"2002","journal-title":"Neurosci. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Loving, B.A., and Bruce, K.D. (2020). Lipid and Lipoprotein Metabolism in Microglia. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.00393"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1161\/CIRCULATIONAHA.106.676890","article-title":"Subendothelial Lipoprotein Retention as the Initiating Process in Atherosclerosis","volume":"116","author":"Tabas","year":"2007","journal-title":"Circulation"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nn0403-345","article-title":"Alzheimer\u2019s disease: The cholesterol connection","volume":"6","author":"Puglielli","year":"2003","journal-title":"Nat. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7965","DOI":"10.3390\/nu7095374","article-title":"Phytosterols, Phytostanols, and Lipoprotein Metabolism","volume":"7","author":"Gylling","year":"2015","journal-title":"Nutrients"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Nunes, V.S., da Silva, E.J., Ferreira Gda, S., de Assis, S.I.S., Cazita, P.M., Nakandakare, E.R., de Souza Zago, V.H., de Faria, E.C., and Quint\u00e3o, E.C.R. (2022). The Plasma Distribution of Non-cholesterol Sterol Precursors and Products of Cholesterol Synthesis and Phytosterols Depend on HDL Concentration. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.723555"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.biochi.2012.09.025","article-title":"24S-hydroxycholesterol in plasma: A marker of cholesterol turnover in neurodegenerative diseases","volume":"95","author":"Leoni","year":"2013","journal-title":"Biochimie"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1177\/1352458513499421","article-title":"Oxysterols and cholesterol precursors correlate to magnetic resonance imaging measures of neurodegeneration in multiple sclerosis","volume":"20","author":"Killestein","year":"2014","journal-title":"Mult. Scler. J."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Pineda-Torra, I., Siddique, S., Waddington, K.E., Farrell, R., and Jury, E.C. (2021). Disrupted Lipid Metabolism in Multiple Sclerosis: A Role for Liver X Receptors?. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.639757"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1084\/jem.20171576","article-title":"Cholesterol negatively regulates IL-9\u2013producing CD8+ T cell differentiation and antitumor activity","volume":"215","author":"Ma","year":"2018","journal-title":"J. Exp. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1093\/brain\/122.11.2089","article-title":"Multiple sclerosis: B- and T-cell responses to the ex-tracellular domain of the myelin oligodendrocyte glycoprotein","volume":"122","author":"Lindert","year":"1999","journal-title":"Brain"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Liu, R., Du, S., Zhao, L., Jain, S., Sahay, K., Rizvanov, A., Lezhnyova, V., Khaibullin, T., Martynova, E., and Khaiboullina, S. (2022). Autoreactive lymphocytes in multiple sclerosis: Pathogenesis and treatment target. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.996469"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e162731","DOI":"10.1172\/JCI162731","article-title":"Pathogenic myelin-specific antibodies in multiple sclerosis target conformational proteolipid protein 1\u2013anchored membrane domains","volume":"133","author":"Owens","year":"2023","journal-title":"J. Clin. Investig."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/j.semarthrit.2016.09.010","article-title":"Relevance of antiphospholipid antibodies in multiple sclerosis: A systematic review and meta analysis","volume":"46","author":"Merashli","year":"2017","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.jaci.2005.03.023","article-title":"Antibody responses against galactocerebroside are potential stage-specific biomarkers in multiple sclerosis","volume":"116","author":"Menge","year":"2005","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_47","first-page":"94","article-title":"Serum IgG and IgM ganglioside GM1 antibodies in patients with multiple sclerosis","volume":"57","author":"Zaprianova","year":"2004","journal-title":"Ideggyogy. Sz."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/S0165-5728(03)00131-0","article-title":"Antibodies to sulfatide in cerebrospinal fluid of patients with multiple sclerosis","volume":"139","author":"Ilyas","year":"2003","journal-title":"J. Neuroimmunol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Podbielska, M., Ariga, T., and Pokryszko-Dragan, A. (2022). Sphingolipid Players in Multiple Sclerosis: Their Influence on the Initiation and Course of the Disease. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23105330"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.addr.2020.04.009","article-title":"Sphingolipids as prognostic biomarkers of neurodegeneration, neuroinflammation, and psychiatric diseases and their emerging role in lipidomic investigation methods","volume":"159","author":"Luo","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1016\/S0140-6736(21)00244-0","article-title":"Sphingosine 1-phosphate receptor modulators in multiple sclerosis and other conditions","volume":"398","author":"McGinley","year":"2021","journal-title":"Lancet"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s40263-021-00798-w","article-title":"Sphingosine 1-Phosphate Receptor Modulators for Multiple Sclerosis","volume":"35","author":"Roy","year":"2021","journal-title":"CNS Drugs"},{"key":"ref_53","first-page":"1557","article-title":"Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis: Up to 5 years of follow-up in the DAYBREAK open-label extension trial","volume":"31","author":"Cree","year":"2022","journal-title":"Mult. Scler. J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"20300","DOI":"10.1038\/s41598-022-21807-y","article-title":"Endo-cannabinoid levels in peripheral blood mononuclear cells of multiple sclerosis patients treated with dimethyl fumarate","volume":"12","author":"Royuela","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"69","DOI":"10.5114\/amsad\/204578","article-title":"High-density lipoprotein cholesterol and multiple sclerosis: A systematic review and meta-analysis","volume":"10","author":"Makris","year":"2025","journal-title":"Arch. Med. Sci.\u2014Atheroscler. Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"188-e4","DOI":"10.1111\/ene.14055","article-title":"Cholesterol and neurodegeneration: Longitudinal changes in serum cholesterol biomarkers are associated with new lesions and gray matter atrophy in multiple sclerosis over 5 years of follow-up","volume":"27","author":"Murali","year":"2020","journal-title":"Eur. J. Neurol."},{"key":"ref_57","first-page":"205521731988272","article-title":"HDL-cholesterol elevation associated with fingolimod and dimethyl fumarate therapies in multiple sclerosis","volume":"5","author":"Kan","year":"2019","journal-title":"Mult. Scler. J.\u2014Exp. Transl. Clin."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2010","DOI":"10.1194\/jlr.M060970","article-title":"Protective associations of HDL with blood-brain barrier injury in multiple sclerosis patients","volume":"56","author":"Fellows","year":"2015","journal-title":"J. Lipid Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e37115","DOI":"10.1097\/MD.0000000000037115","article-title":"Relationship between pattern re-versal visual evoked potential P100 wave latency and dysfunctional HDL in patients with multiple sclerosis subjected to an optic neuritis attack: A case-control study","volume":"103","author":"Vural","year":"2024","journal-title":"Medicine"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"117120","DOI":"10.1016\/j.jns.2020.117120","article-title":"High density lipoprotein cholesterol and apolipoprotein A-I are associated with greater cerebral perfusion in multiple sclerosis","volume":"418","author":"Jakimovski","year":"2020","journal-title":"J. Neurol. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1194\/jlr.M072751","article-title":"Serum lipid profile changes predict neuro-degeneration in interferon-\u03b21a-treated multiple sclerosis patients","volume":"58","author":"Uher","year":"2017","journal-title":"J. Lipid Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1136\/jnnp-2013-307106","article-title":"Apolipoproteins are associated with new MRI lesions and deep grey matter atrophy in clinically isolated syndromes","volume":"85","author":"Browne","year":"2014","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"105870","DOI":"10.1016\/j.jsbmb.2021.105870","article-title":"Oxysterols and multiple sclerosis: Physiopathology, evolutive biomarkers and therapeutic strategy","volume":"210","author":"Vejux","year":"2021","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/s12017-010-8128-4","article-title":"Sphingolipids in Multiple Sclerosis","volume":"12","author":"Jana","year":"2010","journal-title":"Neuromol. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"863","DOI":"10.25122\/jml-2025-0146","article-title":"Dysregulation of the endocannabinoid system\u2014A key factor in the progression of multiple sclerosis?","volume":"18","author":"Paraschiv","year":"2025","journal-title":"J. Med. Life"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Smusz, J., Mojsak, P., Matys, P., Miro\u0144czuk, A., Tarasiuk, J., Grubczak, K., Starosz, A., Kochanowicz, J., Ku\u0142akowska, A., and Ruszczy\u0144ska, K. (2025). Metabolomics in Multiple Sclerosis: Advances, Challenges, and Clinical Perspectives\u2014A Systematic Review. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26189207"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Clayton, P., Hill, M., Bogoda, N., Subah, S., and Venkatesh, R. (2021). Palmitoylethanolamide: A natural compound for health management. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22105305"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.neulet.2015.08.054","article-title":"Anti-annexin antibodies, cholesterol levels and disability in multiple sclerosis","volume":"606","author":"Mandoj","year":"2015","journal-title":"Neurosci. Lett."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1093\/aje\/152.11.1056","article-title":"Dietary Fat in Relation to Risk of Multiple Sclerosis among Two Large Cohorts of Women","volume":"152","author":"Zhang","year":"2000","journal-title":"Am. J. Epidemiol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Ort\u00ed, J.E.d.l.R., Armero, J.L.P., Cuerda-Ballester, M., Sanchis-Sanchis, C.E., Navarro-Illana, E., Lajara-Romance, J.M., Benlloch, M., Ceron, J.J., Tvarijonaviciute, A., and Proa\u00f1o, B. (2023). Lipid Profile in Multiple Sclerosis: Functional Capacity and Therapeutic Potential of Its Regulation after Intervention with Epigallocatechin Gallate and Coconut Oil. Foods, 12.","DOI":"10.3390\/foods12203730"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1007\/s00415-020-10119-8","article-title":"An atlas on risk factors for multiple sclerosis: A Mendelian randomization study","volume":"268","author":"Yuan","year":"2021","journal-title":"J. Neurol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1161\/ATVBAHA.116.307023","article-title":"Central nervous system lipoproteins: ApoE and regulation of cholesterol metabolism","volume":"36","author":"Mahley","year":"2016","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"113634","DOI":"10.1016\/j.biopha.2022.113634","article-title":"Leveraging knowledge of HDLs major protein ApoA1: Structure, function, mutations, and potential therapeutics","volume":"154","author":"Bhale","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.biopsych.2017.03.003","article-title":"Apolipoprotein E, Receptors, and Modulation of Alzheimer\u2019s Disease","volume":"83","author":"Zhao","year":"2018","journal-title":"Biol. Psychiatry"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1034\/j.1600-0404.2002.01334.x","article-title":"Blood cholesterol and MRI activity in first clinical episode suggestive of multiple sclerosis","volume":"106","author":"Giubilei","year":"2002","journal-title":"Acta Neurol. Scand."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1007\/s13760-024-02676-w","article-title":"Lipid and brain volumetric measures in multiple sclerosis patients: Findings from a large observational study","volume":"124","author":"Lorincz","year":"2024","journal-title":"Acta Neurol. Belg."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1111\/j.1365-2990.1994.tb01174.x","article-title":"Low density lipoprotein uptake by macrophages in multiple sclerosis plaques: Implications for pathogenesis","volume":"20","author":"Newcombe","year":"1994","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1615\/CritRevImmunol.2018026483","article-title":"How Oxidized Low-Density Lipoprotein Activates Inflammatory Responses","volume":"38","author":"Rhoads","year":"2018","journal-title":"Crit. Rev. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1155\/2013\/567162","article-title":"New markers of early cardiovascular risk in multiple sclerosis patients: Oxidized-LDL correlates with clinical staging","volume":"34","author":"Palavra","year":"2013","journal-title":"Dis. Markers"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"103133","DOI":"10.1016\/j.msard.2021.103133","article-title":"Cardiovascular risk estimated in individuals with multiple sclerosis: A case-control study","volume":"54","author":"Damasceno","year":"2021","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Ge, Z., Hu, Y., Kan, W., Li, L., Xu, J., Zhang, Y., Zheng, N., Wang, G., and Du, J. (2025). Lipid metabolic dysregulation-induced neuroinflammation in the pathophysiology of major depressive disorder. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1625087"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.jneuroim.2014.10.010","article-title":"A role for Apolipoprotein A-I in the pathogenesis of multiple sclerosis","volume":"277","author":"Meyers","year":"2014","journal-title":"J. Neuroimmunol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Gardner, L.A., and Levin, M.C. (2015). Importance of Apolipoprotein A-I in Multiple Sclerosis. Front. Pharmacol., 6.","DOI":"10.3389\/fphar.2015.00278"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"102389","DOI":"10.1016\/j.msard.2020.102389","article-title":"Apolipoproteins AI and E are associated with neuroaxonal injury to gray matter in multiple sclerosis","volume":"45","author":"McComb","year":"2020","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"184042","DOI":"10.1155\/2012\/184042","article-title":"Dyslipidemia and Blood-Brain Barrier Integrity in Alzheimer\u2019s Disease","volume":"2012","author":"Bowman","year":"2012","journal-title":"Curr. Gerontol. Geriatr. Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1007\/s11481-020-09937-4","article-title":"Lipid Profile Alterations during Fingolimod Treatment in Multiple Sclerosis Patients","volume":"15","author":"Rauma","year":"2020","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"105530","DOI":"10.1016\/j.msard.2024.105530","article-title":"Serum lipids and cognitive outcomes in multiple sclerosis; a systematic review and meta-analysis","volume":"85","author":"Sanaie","year":"2024","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Bahr, L.S., Bellmann-Strobl, J., Koppold, D.A., Rust, R., Schmitz-H\u00fcbsch, T., Olszewska, M., Stadlbauer, J., Bock, M., Scheel, M., and Chien, C. (2025). Fasting, ketogenic, and anti-inflammatory diets in multiple sclerosis: A randomized controlled trial with 18-month follow-up. BMC Nutr., 11.","DOI":"10.1186\/s40795-025-01156-5"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Martinez, A.S., Bastian, A.J., Shemirani, F., Titcomb, T.J., Bisht, B., Darling, W.G., Ramanathan, M., Shittu, M., Gill, C.M., and Snetselaar, L.G. (2025). Effects of a Multimodal Lifestyle Intervention on Cardiometabolic Markers in People with Progressive Multiple Sclerosis: A Secondary Analysis of a Pilot Study. Nutrients, 17.","DOI":"10.3390\/nu17071163"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"16195","DOI":"10.1038\/s41598-024-66448-5","article-title":"High-intensity interval training improves bone remodeling, lipid profile, and physical function in multiple sclerosis patients","volume":"14","author":"Amato","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_91","first-page":"e18092","article-title":"The Effectiveness of Statins as Potential Therapy for Multiple Sclerosis: A Systematic Review of Randomized Controlled trials","volume":"13","author":"Zakhary","year":"2021","journal-title":"Cureus"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.phrs.2014.03.004","article-title":"Role of statins in the treatment of multiple sclerosis","volume":"87","author":"Ciurleo","year":"2014","journal-title":"Pharmacol. Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s40263-015-0239-x","article-title":"Statin Treatment in Multiple Sclerosis: A Systematic Review and Meta-Analysis","volume":"29","author":"Tsakiri","year":"2015","journal-title":"CNS Drugs"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/S1474-4422(11)70144-2","article-title":"Simvastatin as add-on therapy to interferon beta-1a for relapsing-remitting multiple sclerosis (SIMCOMBIN study): A placebo-controlled randomised phase 4 trial","volume":"10","author":"Sorensen","year":"2011","journal-title":"Lancet Neurol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1016\/S0140-6736(13)62242-4","article-title":"Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): A randomised, placebo-controlled, phase 2 trial","volume":"383","author":"Chataway","year":"2014","journal-title":"Lancet"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1001\/archneurol.2012.465","article-title":"Inhibition of Interferon-beta Responses in Multiple Sclerosis Immune Cells Associated With High-Dose Statins","volume":"69","author":"Feng","year":"2012","journal-title":"Arch. Neurol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"e1130","DOI":"10.1212\/NXI.0000000000001130","article-title":"Assessing Neurofilaments as Biomarkers of Neuroprotection in Progressive Multiple Sclerosis","volume":"9","author":"Williams","year":"2022","journal-title":"Neurol.\u2014Neuroimmunol. Neuroinflamm."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/s40001-024-01700-2","article-title":"Role of fenofibrate in multiple sclerosis","volume":"29","author":"Abulaban","year":"2024","journal-title":"Eur. J. Med. Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"11193","DOI":"10.1002\/anie.201603746","article-title":"Second-Generation Non-Covalent NAAA Inhibitors are Protective in a Model of Multiple Sclerosis","volume":"55","author":"Migliore","year":"2016","journal-title":"Angew. Chem.-Int. Ed."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/2\/812\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T09:07:19Z","timestamp":1768381639000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/2\/812"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,14]]},"references-count":99,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["ijms27020812"],"URL":"https:\/\/doi.org\/10.3390\/ijms27020812","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,14]]}}}