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Cited by 13Multiple Sclerosis Research StudiesNeurogenesis and neuroplasticity mechanismsNeuroinflammation and Neurodegeneration Mechanisms

White Matter in Crisis: Oligodendrocytes and the Pathophysiology of Multiple Sclerosis

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García-Domínguez, Mario·2025·Cells
DOI 10.3390/cells14181408PMC PMC12468040
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Abstract

Multiple sclerosis is a chronic, immune-mediated neurodegenerative disorder of the central nervous system, characterized by widespread demyelination, axonal injury, and progressive neurological impairment. The pathophysiology of multiple sclerosis involves complex interactions between immune cells and central nervous system resident cells, with oligodendrocytes (the myelin-producing glial cells) occupying a central role in both the disease’s onset and progression. Oligodendrocyte dysfunction, including diminished regenerative capacity, heightened vulnerability to inflammatory cytokines, and increased susceptibility to oxidative stress, contributes significantly to the failure of remyelination observed in chronic multiple sclerosis lesions. Key factors such as microglial activation, T-cell-mediated cytotoxicity, and altered signaling pathways affecting oligodendrocyte progenitor cell maturation are explored in depth. Some therapeutic strategies under investigation encompass the use of pharmacological agents, cell-based interventions, and modulation of both the extracellular matrix and the immune microenvironment. Advancing our understanding of oligodendrocyte biology, along with the intrinsic and extrinsic factors that impede effective remyelination, is critical for the development of innovative, targeted therapies aimed at attenuating neurodegeneration and enhancing long-term clinical outcomes in patients with multiple sclerosis.

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  • In demyelinating and dysmyelinating models, phosphoinositide distributions within white matter tracts are altered.

    “In demyelinating and dysmyelinating models, phosphoinositide distributions within white matter tracts are altered [85–87]”

    From PLCγ2 deficiency compromises systemic immune tolerance and erodes myelin homeostasis while enhancing oxidative metabolism in the mouse brain (2026) · cites this paper as [85]

    The Introduction describes demyelinated plaques in white matter, but does not discuss phosphoinositide distributions. Searches for “phosphoinositide” and for lipid distribution in dysmyelinating models found only a mention of phosphoinositide 3-kinase in a therapeutic table (Section 4.3, page unavailable), not the claimed change within white matter tracts. (LLM, conf=0.76)

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  1. [1]Haki M. Al-Biati H.A. Al-Tameemi Z.S. Ali I.S. Al-Hussaniy H.A. Review of multiple sclerosis: Epidemiology, etiology, pathophysiology, and treatment Medicine 2024 103 37297 10.1097/MD.0000000000037297 PMC10883637 38394496 · DOI
  2. [2]Coyle P.K. What Can We Learn from Sex Differences in MS? J. Pers. Med. 2021 11 1006 10.3390/jpm11101006 34683148 PMC8537319 · DOI
  3. [3]Prosperini L. Lucchini M. Ruggieri S. Tortorella C. Haggiag S. Mirabella M. Pozzilli C. Gasperini C. Shift of multiple sclerosis onset towards older age J. Neurol. Neurosurg. Psychiatry 2022 2022 329049 10.1136/jnnp-2022-329049 35477891 · DOI
  4. [4]Sabel C.E. Pearson J.F. Mason D.F. Willoughby E. Abernethy D.A. Taylor B.V. The latitude gradient for multiple sclerosis prevalence is established in the early life course Brain 2021 144 2038 2046 10.1093/brain/awab104 33704407 · DOI
  5. [5]Olsson T. Barcellos L.F. Alfredsson L. Interactions between genetic, lifestyle and environmental risk factors for multiple sclerosis Nat. Rev. Neurol. 2017 13 25 36 10.1038/nrneurol.2016.187 27934854 · DOI
  6. [6]Waubant E. Lucas R. Mowry E. Graves J. Olsson T. Alfredsson L. Langer-Gould A. Environmental and genetic risk factors for MS: An integrated review Ann. Clin. Transl. Neurol. 2019 6 1905 1922 10.1002/acn3.50862 31392849 PMC6764632 · DOI
  7. [7]Oudejans E. Luchicchi A. Strijbis E.M.M. Geurts J.J.G. van Dam A.M. Is MS affecting the CNS only? Lessons from clinic to myelin pathophysiology Neurol. Neuroimmunol. Neuroinflamm. 2020 8 914 10.1212/NXI.0000000000000914 33234720 PMC7803330 · DOI
  8. [8]Stavropoulou De Lorenzo S. Bakirtzis C. Konstantinidou N. Kesidou E. Parissis D. Evangelopoulos M.E. Elsayed D. Hamdy E. Said S. Grigoriadis N. How Early Is Early Multiple Sclerosis? J. Clin. Med. 2023 13 214 10.3390/jcm13010214 38202221 PMC10780129 · DOI
  9. [9]Portaccio E. Magyari M. Havrdova E.K. Ruet A. Brochet B. Scalfari A. Di Filippo M. Tur C. Montalban X. Amato M.P. Multiple sclerosis: Emerging epidemiological trends and redefining the clinical course Lancet Reg. Health Eur. 2024 44 100977 10.1016/j.lanepe.2024.100977 39444703 PMC11496978 · DOI
  10. [10]Benedict R.H.B. Amato M.P. DeLuca J. Geurts J.J.G. Cognitive impairment in multiple sclerosis: Clinical management, MRI, and therapeutic avenues Lancet Neurol. 2020 19 860 871 10.1016/S1474-4422(20)30277-5 32949546 PMC10011205 · DOI
  11. [11]Pintér A. Cseh D. Sárközi A. Illigens B.M. Siepmann T. Autonomic Dysregulation in Multiple Sclerosis Int. J. Mol. Sci. 2015 16 16920 16952 10.3390/ijms160816920 26213927 PMC4581177 · DOI
  12. [12]Liu Z. Liao Q. Wen H. Zhang Y. Disease modifying therapies in relapsing-remitting multiple sclerosis: A systematic review and network meta-analysis Autoimmun. Rev. 2021 20 102826 10.1016/j.autrev.2021.102826 33878488 · DOI
  13. [13]Ziemssen T. Bhan V. Chataway J. Chitnis T. Campbell Cree B.A. Havrdova E.K. Kappos L. Labauge P. Miller A. Nakahara J. Secondary Progressive Multiple Sclerosis: A Review of Clinical Characteristics, Definition, Prognostic Tools, and Disease-Modifying Therapies Neurol. Neuroimmunol. Neuroinflamm. 2022 10 200064 10.1212/NXI.0000000000200064 PMC9682625 36414428 · DOI
  14. [14]Sempik I. Dziadkowiak E. Moreira H. Zimny A. Pokryszko-Dragan A. Primary Progressive Multiple Sclerosis-A Key to Understanding and Managing Disease Progression Int. J. Mol. Sci. 2024 25 8751 10.3390/ijms25168751 39201438 PMC11354232 · DOI
  15. [15]Tullman M.J. Oshinsky R.J. Lublin F.D. Cutter G.R. Clinical characteristics of progressive relapsing multiple sclerosis Mult. Scler. 2004 10 451 454 10.1191/1352458504ms1059oa 15327045 · DOI
  16. [16]Arredondo-Robles A.V. Rodríguez-López K.P. Ávila-Avilés R.D. Clinical Management in Multiple Sclerosis Neuroglia 2025 6 6 10.3390/neuroglia6010006 · DOI
  17. [17]Huang W.J. Chen W.W. Zhang X. Multiple sclerosis: Pathology, diagnosis and treatments Exp. Ther. Med. 2017 13 3163 3166 10.3892/etm.2017.4410 28588671 PMC5450788 · DOI
  18. [18]Multz R.A. Jamshidi P. Ahrendsen J.T. Multiple sclerosis: A practical review for pathologists J. Pathol. Transl. Med. 2025 59 203 213 10.4132/jptm.2025.05.20 40574276 PMC12264475 · DOI
  19. [19]Balasa R. Barcutean L. Mosora O. Manu D. Reviewing the Significance of Blood–Brain Barrier Disruption in Multiple Sclerosis Pathology and Treatment Int. J. Mol. Sci. 2021 22 8370 10.3390/ijms22168370 34445097 PMC8395058 · DOI
  20. [20]Zierfuss B. Larochelle C. Prat A. Blood–brain barrier dysfunction in multiple sclerosis: Causes, consequences, and potential effects of therapies Lancet Neurol. 2024 23 95 109 10.1016/S1474-4422(23)00377-0 38101906 · DOI
  21. [21]Suknjaja V. Sakalaš L. Ilin M. EARLY ONSET OF MULTIPLE SCLEROSIS–CLINICAL FEATURES Acta Clin. Croat. 2024 63 23 28 10.20471/acc.2024.63.01.3 PMC11827390 39959328 · DOI
  22. [22]Murtonen A. Lehto J.T. Sumelahti M.L. End of life in multiple sclerosis: Disability, causes and place of death among cases diagnosed from 1981 to 2010 in Pirkanmaa hospital district in Western Finland Mult. Scler. Relat. Disord. 2021 54 103139 10.1016/j.msard.2021.103139 34273609 · DOI
  23. [23]Miyata S. Wake H. Editorial: Oligodendrocytes: From their development to function and dysfunction Front. Cell Neurosci. 2024 18 1376931 10.3389/fncel.2024.1376931 38515788 PMC10955062 · DOI
  24. [24]Wellman S.M. Cambi F. Kozai T.D. The role of oligodendrocytes and their progenitors on neural interface technology: A novel perspective on tissue regeneration and repair Biomaterials 2018 183 200 217 10.1016/j.biomaterials.2018.08.046 30172245 PMC6469877 · DOI
  25. [25]Nave K.A. Asadollahi E. Sasmita A. Expanding the function of oligodendrocytes to brain energy metabolism Curr. Opin. Neurobiol. 2023 83 102782 10.1016/j.conb.2023.102782 37703600 · DOI
  26. [26]Meyer-Arndt L. Kerkering J. Kuehl T. Infante A.G. Paul F. Rosiewicz K.S. Siffrin V. Alisch M. Inflammatory Cytokines Associated with Multiple Sclerosis Directly Induce Alterations of Neuronal Cytoarchitecture in Human Neurons J. Neuroimmune Pharmacol. 2023 18 145 159 10.1007/s11481-023-10059-w 36862362 PMC10485132 · DOI
  27. [27]Silva B.D. Viero F.T. Rodrigues P. Trevisan G. Nitric oxide involvement in the disability and active disease of multiple sclerosis: Systematic review and meta-analysis Nitric Oxide 2024 145 8 20 10.1016/j.niox.2024.01.006 38331311 · DOI
  28. [28]Piñar-Morales R. Durán R. Bautista-García A. García-Mansilla M.J. Aliaga-Gaspar P. Vives-Montero F. Barrero-Hernández F.J. The impact of oxidative stress on symptoms associated with multiple sclerosis Sci. Rep. 2025 15 22983 10.1038/s41598-025-07429-0 40596531 PMC12215555 · DOI
  29. [29]Lulu S. Waubant E. Humoral-targeted immunotherapies in multiple sclerosis Neurotherapeutics 2013 10 34 43 10.1007/s13311-012-0164-3 23208729 PMC3557366 · DOI
  30. [30]Akay L.A. Effenberger A.H. Tsai L.H. Cell of all trades: Oligodendrocyte precursor cells in synaptic, vascular, and immune function Genes. Dev. 2021 35 180 198 10.1101/gad.344218.120 33526585 PMC7849363 · DOI
  31. [31]Tepavčević V. Lubetzki C. Oligodendrocyte progenitor cell recruitment and remyelination in multiple sclerosis: The more, the merrier? Brain 2022 145 4178 4192 10.1093/brain/awac307 36093726 · DOI
  32. [32]Ma Q. Shams H. Didonna A. Baranzini S.E. Cree B.A.C. Hauser S.L. Henry R.G. Oksenberg J.R. Integration of epigenetic and genetic profiles identifies multiple sclerosis disease-critical cell types and genes Commun. Biol. 2023 6 342 10.1038/s42003-023-04713-5 36997638 PMC10063586 · DOI
  33. [33]Koutsoudaki P.N. Papadopoulos D. Passias P.G. Koutsoudaki P. Gorgoulis V.G. Cellular senescence and failure of myelin repair in multiple sclerosis Mech. Ageing Dev. 2020 192 111366 10.1016/j.mad.2020.111366 32991921 · DOI
  34. [34]Jäkel S. Agirre E. Mendanha Falcão A. van Bruggen D. Lee K.W. Knuesel I. Malhotra D. Ffrench-Constant C. Williams A. Castelo-Branco G. Altered human oligodendrocyte heterogeneity in multiple sclerosis Nature 2019 566 543 547 10.1038/s41586-019-0903-2 30747918 PMC6544546 · DOI · Paper page
  35. [35]Zveik O. Rechtman A. Ganz T. Vaknin-Dembinsky A. The interplay of inflammation and remyelination: Rethinking MS treatment with a focus on oligodendrocyte progenitor cells Mol. Neurodegener. 2024 19 53 10.1186/s13024-024-00742-8 38997755 PMC11245841 · DOI
  36. [36]You Y. Gupta V. The Extracellular Matrix and Remyelination Strategies in Multiple Sclerosis eNeuro 2018 5 e0435-17.2018 10.1523/ENEURO.0435-17.2018 PMC5898789 29662941 · DOI
  37. [37]Gaesser J.M. Fyffe-Maricich S.L. Intracellular signaling pathway regulation of myelination and remyelination in the CNS Exp. Neurol. 2016 283 501 511 10.1016/j.expneurol.2016.03.008 26957369 PMC5010983 · DOI
  38. [38]Simkins T.J. Duncan G.J. Bourdette D. Chronic Demyelination and Axonal Degeneration in Multiple Sclerosis: Pathogenesis and Therapeutic Implications Curr. Neurol. Neurosci. Rep. 2021 21 26 10.1007/s11910-021-01110-5 33835275 · DOI
  39. [39]Looser Z.J. Faik Z. Ravotto L. Zanker H.S. Jung R.B. Werner H.B. Ruhwedel T. Möbius W. Bergles D.E. Barros L.F. Oligodendrocyte-axon metabolic coupling is mediated by extracellular K+ and maintains axonal health Nat. Neurosci. 2024 27 433 448 10.1038/s41593-023-01558-3 38267524 PMC10917689 · DOI
  40. [40]Li S. Sheng Z.H. Oligodendrocyte-derived transcellular signaling regulates axonal energy metabolism Curr. Opin. Neurobiol. 2023 80 102722 10.1016/j.conb.2023.102722 37028201 PMC10225329 · DOI
  41. [42]Wu X. Wang S. Xue T. Tan X. Li J. Chen Z. Wang Z. Disease-modifying therapy in progressive multiple sclerosis: A systematic review and network meta-analysis of randomized controlled trials Front. Neurol. 2024 15 1295770 10.3389/fneur.2024.1295770 38529035 PMC10962394 · DOI
  42. [43]Plemel J.R. Liu W.Q. Yong V.W. Remyelination therapies: A new direction and challenge in multiple sclerosis Nat. Rev. Drug Discov. 2017 16 617 634 10.1038/nrd.2017.115 28685761 · DOI
  43. [44]Sharma T. Mehan S. Tiwari A. Khan Z. Gupta G.D. Narula A.S. Targeting Oligodendrocyte Dynamics and Remyelination: Emerging Therapies and Personalized Approaches in Multiple Sclerosis Management Curr. Neurovasc. Res. 2025 21 359 417 10.2174/0115672026336440240822063430 39219420 · DOI
  44. [45]Manousi A. Göttle P. Reiche L. Cui Q.L. Healy L.M. Akkermann R. Gruchot J. Schira-Heinen J. Antel J.P. Hartung H.P. Identification of novel myelin repair drugs by modulation of oligodendroglial differentiation competence eBioMedicine 2021 65 103276 10.1016/j.ebiom.2021.103276 33714029 PMC7970057 · DOI
  45. [46]Medina-Rodríguez E.M. Bribián A. Boyd A. Palomo V. Pastor J. Lagares A. Gil C. Martínez A. Williams A. de Castro F. Promoting in vivo remyelination with small molecules: A neuroreparative pharmacological treatment for Multiple Sclerosis Sci. Rep. 2017 7 43545 10.1038/srep43545 28256546 PMC5335257 · DOI
  46. [47]Christodoulou M.V. Petkou E. Atzemoglou N. Gkorla E. Karamitrou A. Simos Y.V. Bellos S. Bekiari C. Kouklis P. Konitsiotis S. Cell replacement therapy with stem cells in multiple sclerosis, a systematic review Hum. Cell 2024 37 9 53 10.1007/s13577-023-01006-1 37985645 PMC10764451 · DOI
  47. [48]Paroni M. Maltese V. De Simone M. Ranzani V. Larghi P. Fenoglio C. Pietroboni A.M. De Riz M.A. Crosti M.C. Maglie S. Recognition of viral and self-antigens by TH1 and TH1/TH17 central memory cells in patients with multiple sclerosis reveals distinct roles in immune surveillance and relapses J. Allergy Clin. Immunol. 2017 140 797 808 10.1016/j.jaci.2016.11.045 28237728 · DOI · Paper page
  48. [49]Lai S. Wu X. Liu Y. Liu B. Wu H. Ma K. Interaction between Th17 and central nervous system in multiple sclerosis Brain Behav. Immun. Health 2024 43 100928 10.1016/j.bbih.2024.100928 39845807 PMC11751430 · DOI
  49. [50]Chastain E.M. Duncan D.S. Rodgers J.M. Miller S.D. The role of antigen presenting cells in multiple sclerosis Biochim. Biophys. Acta 2011 1812 265 274 10.1016/j.bbadis.2010.07.008 20637861 PMC2970677 · DOI
  50. [51]Sonar S.A. Lal G. Differentiation and Transmigration of CD4 T Cells in Neuroinflammation and Autoimmunity Front. Immunol. 2017 8 1695 10.3389/fimmu.2017.01695 29238350 PMC5712560 · DOI
  51. [52]Li R. Li H. Yang X. Hu H. Liu P. Liu H. Crosstalk between dendritic cells and regulatory T cells: Protective effect and therapeutic potential in multiple sclerosis Front. Immunol. 2022 13 970508 10.3389/fimmu.2022.970508 36177043 PMC9513370 · DOI
  52. [53]Ma M. Jiang W. Zhou R. DAMPs and DAMP-sensing receptors in inflammation and diseases Immunity 2024 57 752 771 10.1016/j.immuni.2024.03.002 38599169 · DOI
  53. [54]Lassmann H. Ransohoff R.M. The CD4-Th1 model for multiple sclerosis: A critical re-appraisal Trends Immunol. 2004 25 132 137 10.1016/j.it.2004.01.007 15036040 · DOI
  54. [55]Catenacci R.B. Galleguillos D. Rhodes A. Phillips S. Calabresi P.A. MHC class I and II expression and induction in oligodendrocytes varies with age Sci. Rep. 2025 15 18309 10.1038/s41598-025-03089-2 40419671 PMC12106765 · DOI
  55. [56]Moser T. Akgün K. Proschmann U. Sellner J. Ziemssen T. The role of TH17 cells in multiple sclerosis: Therapeutic implications Autoimmun. Rev. 2020 19 102647 10.1016/j.autrev.2020.102647 32801039 · DOI
  56. [58]Setiadi A.F. Abbas A.R. Jeet S. Wong K. Bischof A. Peng I. Lee J. Bremer M. Eggers E.L. DeVoss J. IL-17A is associated with the breakdown of the blood-brain barrier in relapsing-remitting multiple sclerosis J. Neuroimmunol. 2019 332 147 154 10.1016/j.jneuroim.2019.04.011 31034962 · DOI
  57. [59]Behrens M. Comabella M. Lünemann J.D. EBV-specific T-cell immunity: Relevance for multiple sclerosis Front. Immunol. 2024 15 1509927 10.3389/fimmu.2024.1509927 39776919 PMC11703957 · DOI
  58. [60]Thomas O.G. Olsson T. Mimicking the brain: Epstein-Barr virus and foreign agents as drivers of neuroimmune attack in multiple sclerosis Front. Immunol. 2023 14 1304281 10.3389/fimmu.2023.1304281 38022632 PMC10655090 · DOI
  59. [61]Comi G. Bar-Or A. Lassmann H. Uccelli A. Hartung H.P. Montalban X. Sørensen P.S. Hohlfeld R. Hauser S.L. Expert Panel of the 27th Annual Meeting of the European Charcot Foundation. Role of B Cells in Multiple Sclerosis and Related Disorders Ann. Neurol. 2021 89 13 23 10.1002/ana.25927 33091175 PMC8007167 · DOI
  60. [62]Wekerle H. B cells in multiple sclerosis Autoimmunity 2017 50 57 60 10.1080/08916934.2017.1281914 28166681 · DOI
  61. [63]Arneth B.M. Impact of B cells to the pathophysiology of multiple sclerosis J. Neuroinflamm. 2019 16 128 10.1186/s12974-019-1517-1 31238945 PMC6593488 · DOI
  62. [64]Negron A. Stüve O. Forsthuber T.G. Ectopic Lymphoid Follicles in Multiple Sclerosis: Centers for Disease Control? Front. Neurol. 2020 11 607766 10.3389/fneur.2020.607766 33363512 PMC7753025 · DOI · Paper page
  63. [65]Bonnan M. Intrathecal IgG synthesis: A resistant and valuable target for future multiple sclerosis treatments Mult. Scler. Int. 2015 2015 296184 10.1155/2015/296184 25653878 PMC4306411 · DOI
  64. [66]Saez-Calveras N. Stuve O. The role of the complement system in Multiple Sclerosis: A review Front. Immunol. 2022 13 970486 10.3389/fimmu.2022.970486 36032156 PMC9399629 · DOI
  65. [67]Ingram G. Loveless S. Howell O.W. Hakobyan S. Dancey B. Harris C.L. Robertson N.P. Neal J.W. Morgan B.P. Complement activation in multiple sclerosis plaques: An immunohistochemical analysis Acta Neuropathol. Commun. 2014 2 53 10.1186/2051-5960-2-53 24887075 PMC4048455 · DOI
  66. [68]Morille J. Mandon M. Rodriguez S. Roulois D. Leonard S. Garcia A. Wiertlewski S. Le Page E. Berthelot L. Nicot A. Multiple Sclerosis CSF Is Enriched With Follicular T Cells Displaying a Th1/Eomes Signature Neurol. Neuroimmunol. Neuroinflamm. 2022 9 200033 10.1212/NXI.0000000000200033 PMC9585484 36266053 · DOI
  67. [69]Jones B.E. Maerz M.D. Buckner J.H. IL-6: A cytokine at the crossroads of autoimmunity Curr. Opin. Immunol. 2018 55 9 14 10.1016/j.coi.2018.09.002 30248523 PMC6286200 · DOI
  68. [70]Varghese J.F. Kaskow B.J. von Glehn F. Case J. Li Z. Julé A.M. Berdan E. Ho Sui S.J. Hu Y. Krishnan R. Human regulatory memory B cells defined by expression of TIM-1 and TIGIT are dysfunctional in multiple sclerosis Front. Immunol. 2024 15 1360219 10.3389/fimmu.2024.1360219 38745667 PMC11091236 · DOI
  69. [72]Cannella B. Raine C.S. The adhesion molecule and cytokine profile of multiple sclerosis lesions Ann. Neurol. 1995 37 424 435 10.1002/ana.410370404 7536402 · DOI
  70. [73]Elovaara I. Ukkonen M. Leppäkynnäs M. Lehtimäki T. Luomala M. Peltola J. Dastidar P. Adhesion molecules in multiple sclerosis: Relation to subtypes of disease and methylprednisolone therapy Arch. Neurol. 2000 57 546 551 10.1001/archneur.57.4.546 10768630 · DOI
  71. [74]Schwab N. Schneider-Hohendorf T. Wiendl H. Therapeutic uses of anti-α4-integrin (anti-VLA-4) antibodies in multiple sclerosis Int. Immunol. 2015 27 47 53 10.1093/intimm/dxu096 25326459 · DOI
  72. [75]Bö L. Peterson J.W. Mørk S. Hoffman P.A. Gallatin W.M. Ransohoff R.M. Trapp B.D. Distribution of immunoglobulin superfamily members ICAM-1, -2, -3, and the beta 2 integrin LFA-1 in multiple sclerosis lesions J. Neuropathol. Exp. Neurol. 1996 55 1060 1072 10.1097/00005072-199655100-00006 8858003 · DOI
  73. [76]Yang J. Ran M. Li H. Lin Y. Ma K. Yang Y. Fu X. Yang S. New insight into neurological degeneration: Inflammatory cytokines and blood-brain barrier Front. Mol. Neurosci. 2022 15 1013933 10.3389/fnmol.2022.1013933 36353359 PMC9637688 · DOI
  74. [79]Wimmer I. Tietz S. Nishihara H. Deutsch U. Sallusto F. Gosselet F. Lyck R. Muller W.A. Lassmann H. Engelhardt B. PECAM-1 Stabilizes Blood-Brain Barrier Integrity and Favors Paracellular T-Cell Diapedesis Across the Blood-Brain Barrier During Neuroinflammation Front. Immunol. 2019 10 711 10.3389/fimmu.2019.00711 31024547 PMC6460670 · DOI
  75. [80]Tietz S. Périnat T. Greene G. Enzmann G. Deutsch U. Adams R. Imhof B. Aurrand-Lions M. Engelhardt B. Lack of junctional adhesion molecule (JAM)-B ameliorates experimental autoimmune encephalomyelitis Brain Behav. Immun. 2018 73 3 20 10.1016/j.bbi.2018.06.014 29920328 · DOI
  76. [81]Kim S. Jung U.J. Kim S.R. Role of Oxidative Stress in Blood-Brain Barrier Disruption and Neurodegenerative Diseases Antioxidants 2024 13 1462 10.3390/antiox13121462 39765790 PMC11673141 · DOI
  77. [82]Sun Y. Yu H. Guan Y. Glia Connect Inflammation and Neurodegeneration in Multiple Sclerosis Neurosci. Bull. 2023 39 466 478 10.1007/s12264-023-01034-9 36853544 PMC10043151 · DOI
  78. [83]Zhang X. Chen F. Sun M. Wu N. Liu B. Yi X. Ge R. Fan X. Microglia in the context of multiple sclerosis Front. Neurol. 2023 14 1157287 10.3389/fneur.2023.1157287 37360338 PMC10287974 · DOI
  79. [84]Asadzadeh Manjili F. Yousefi-Ahmadipour A. Kazemi Arababadi M. The roles played by TLR4 in the pathogenesis of multiple sclerosis; A systematic review article Immunol. Lett. 2020 220 63 70 10.1016/j.imlet.2020.02.004 32032617 · DOI
  80. [85]Fan H. Fu Q. Du G. Qin L. Shi X. Wang D. Yang Y. Microglial Mayhem NLRP3 Inflammasome’s Role in Multiple Sclerosis Pathology CNS Neurosci. Ther. 2024 30 70135 10.1111/cns.70135 PMC11652677 39690733 · DOI
  81. [86]Zheng C. Chen J. Chu F. Zhu J. Jin T. Inflammatory Role of TLR-MyD88 Signaling in Multiple Sclerosis Front. Mol. Neurosci. 2020 12 314 10.3389/fnmol.2019.00314 31998072 PMC6965019 · DOI
  82. [87]Timmerman R. Zuiderwijk-Sick E.A. Bajramovic J.J. P2Y6 receptor-mediated signaling amplifies TLR-induced pro-inflammatory responses in microglia Front. Immunol. 2022 13 967951 10.3389/fimmu.2022.967951 36203578 PMC9531012 · DOI
  83. [88]di Penta A. Moreno B. Reix S. Fernandez-Diez B. Villanueva M. Errea O. Escala N. Vandenbroeck K. Comella J.X. Villoslada P. Oxidative stress and proinflammatory cytokines contribute to demyelination and axonal damage in a cerebellar culture model of neuroinflammation PLoS ONE 2013 8 54722 10.1371/journal.pone.0054722 PMC3576396 23431360 · DOI
  84. [89]Smith A.N. Shaughness M. Collier S. Hopkins D. Byrnes K.R. Therapeutic targeting of microglia mediated oxidative stress after neurotrauma Front. Med. 2022 9 1034692 10.3389/fmed.2022.1034692 PMC9671221 36405593 · DOI
  85. [90]Edison P. Astroglial activation: Current concepts and future directions Alzheimers Dement. 2024 20 3034 3053 38305570 PMC11032537
  86. [91]García-Domínguez M. Relationship of S100 Proteins with Neuroinflammation Biomolecules 2025 15 1125 10.3390/biom15081125 40867570 PMC12384525 · DOI
  87. [92]Rao X. Hua F. Zhang L. Lin Y. Fang P. Chen S. Ying J. Wang X. Dual roles of interleukin-33 in cognitive function by regulating central nervous system inflammation J. Transl. Med. 2022 20 369 10.1186/s12967-022-03570-w 35974336 PMC9382782 · DOI
  88. [93]Wiese S. Karus M. Faissner A. Astrocytes as a source for extracellular matrix molecules and cytokines Front. Pharmacol. 2012 3 120 10.3389/fphar.2012.00120 22740833 PMC3382726 · DOI · Paper page
  89. [94]Blake M.R. Gardner R.T. Jin H. Staffenson M.A. Rueb N.J. Barrios A.M. Dudley G.B. Cohen M.S. Habecker B.A. Small Molecules Targeting PTPσ-Trk Interactions Promote Sympathetic Nerve Regeneration ACS Chem. Neurosci. 2022 13 688 699 10.1021/acschemneuro.1c00854 35156811 PMC9112862 · DOI
  90. [95]Hosseini S.M. Alizadeh A. Shahsavani N. Chopek J. Ahlfors J.E. Karimi-Abdolrezaee S. Suppressing CSPG/LAR/PTPσ Axis Facilitates Neuronal Replacement and Synaptogenesis by Human Neural Precursor Grafts and Improves Recovery after Spinal Cord Injury J. Neurosci. 2022 42 3096 3121 10.1523/JNEUROSCI.2177-21.2022 35256527 PMC8994547 · DOI
  91. [96]Domingues H.S. Portugal C.C. Socodato R. Relvas J.B. Oligodendrocyte, Astrocyte, and Microglia Crosstalk in Myelin Development, Damage, and Repair Front. Cell Dev. Biol. 2016 4 71 27551677 PMC4923166
  92. [97]Miron V.E. Franklin R.J. Macrophages and CNS remyelination J. Neurochem. 2014 130 165 171 10.1111/jnc.12705 24601941 · DOI
  93. [98]Lei Z. Lin W. Mechanisms Governing Oligodendrocyte Viability in Multiple Sclerosis and Its Animal Models Cells 2024 13 116 10.3390/cells13020116 38247808 PMC10814231 · DOI
  94. [99]Denic A. Wootla B. Rodriguez M. CD8+ T cells in multiple sclerosis Expert. Opin. Ther. Targets 2013 17 1053 1066 10.1517/14728222.2013.815726 23829711 PMC3928018 · DOI
  95. [100]Saxena A. Bauer J. Scheikl T. Zappulla J. Audebert M. Desbois S. Waisman A. Lassmann H. Liblau R.S. Mars L.T. Cutting edge: Multiple sclerosis-like lesions induced by effector CD8 T cells recognizing a sequestered antigen on oligodendrocytes J. Immunol. 2008 181 1617 1621 10.4049/jimmunol.181.3.1617 18641296 · DOI
  96. [102]Caprariello A.V. Mangla S. Miller R.H. Selkirk S.M. Apoptosis of oligodendrocytes in the central nervous system results in rapid focal demyelination Ann. Neurol. 2012 72 395 405 10.1002/ana.23606 23034912 PMC3464960 · DOI
  97. [103]Prineas J.W. Parratt J.D. Oligodendrocytes and the early multiple sclerosis lesion Ann. Neurol. 2012 72 18 31 10.1002/ana.23634 22829266 · DOI · Paper page
  98. [104]Caprariello A.V. Batt C.E. Zippe I. Romito-DiGiacomo R.R. Karl M. Miller R.H. Apoptosis of Oligodendrocytes during Early Development Delays Myelination and Impairs Subsequent Responses to Demyelination J. Neurosci. 2015 35 14031 14041 10.1523/JNEUROSCI.1706-15.2015 26468203 PMC4604236 · DOI
  99. [105]Hövelmeyer N. Hao Z. Kranidioti K. Kassiotis G. Buch T. Frommer F. von Hoch L. Kramer D. Minichiello L. Kollias G. Apoptosis of oligodendrocytes via Fas and TNF-R1 is a key event in the induction of experimental autoimmune encephalomyelitis J. Immunol. 2005 175 5875 5884 10.4049/jimmunol.175.9.5875 16237080 · DOI
  100. [106]Jurewicz A. Matysiak M. Tybor K. Kilianek L. Raine C.S. Selmaj K. Tumour necrosis factor-induced death of adult human oligodendrocytes is mediated by apoptosis inducing factor Brain 2005 128 2675 2688 10.1093/brain/awh627 16219674 · DOI
  101. [107]Seil F.J. Myelin Antigens and Antimyelin Antibodies Antibodies 2018 7 2 10.3390/antib7010002 31544855 PMC6698820 · DOI
  102. [108]Eliseeva D.D. Zakharova M.N. Myelin Oligodendrocyte Glycoprotein as an Autoantigen in Inflammatory Demyelinating Diseases of the Central Nervous System Biochemistry 2023 88 551 563 10.1134/S0006297923040107 37080940 · DOI
  103. [109]Hedegaard C.J. Chen N. Sellebjerg F. Sørensen P.S. Leslie R.G. Bendtzen K. Nielsen C.H. Autoantibodies to myelin basic protein (MBP) in healthy individuals and in patients with multiple sclerosis: A role in regulating cytokine responses to MBP Immunology 2009 128 e451 e461 10.1111/j.1365-2567.2008.02999.x 19191913 PMC2753924 · DOI
  104. [110]Bittner S. Meuth S.G. Targeting ion channels for the treatment of autoimmune neuroinflammation Ther. Adv. Neurol. Disord. 2013 6 322 336 10.1177/1756285613487782 23997817 PMC3755531 · DOI
  105. [111]Nicaise C. Marneffe C. Bouchat J. Gilloteaux J. Osmotic Demyelination: From an Oligodendrocyte to an Astrocyte Perspective Int. J. Mol. Sci. 2019 20 1124 10.3390/ijms20051124 30841618 PMC6429405 · DOI
  106. [112]Ofengeim D. Ito Y. Najafov A. Zhang Y. Shan B. DeWitt J.P. Ye J. Zhang X. Chang A. Vakifahmetoglu-Norberg H. Activation of necroptosis in multiple sclerosis Cell Rep. 2015 10 1836 1849 10.1016/j.celrep.2015.02.051 25801023 PMC4494996 · DOI · Paper page
  107. [114]Zhou Y. Xiang Y. Liu S. Li C. Dong J. Kong X. Ji X. Cheng X. Zhang L. RIPK3 signaling and its role in regulated cell death and diseases Cell Death Discov. 2024 10 200 10.1038/s41420-024-01957-w 38684668 PMC11059363 · DOI
  108. [115]Xiao M. Gao G. Mu J. Sun Q. Zhao Y. Fan X. MLKL Modulates Necroptosis and Neuroinflammation in a Mouse Model of MS Inflammation 2025 48 10.1007/s10753-025-02323-3 PMC12722336 40601171 · DOI
  109. [116]Faergeman S.L. Evans H. Attfield K.E. Desel C. Kuttikkatte S.B. Sommerlund M. Jensen L.T. Frokiaer J. Friese M.A. Matthews P.M. A novel neurodegenerative spectrum disorder in patients with MLKL deficiency Cell Death Dis. 2020 11 303 10.1038/s41419-020-2494-0 32358523 PMC7195448 · DOI
  110. [117]Huntemer-Silveira A. Patil N. Brickner M.A. Parr A.M. Strategies for Oligodendrocyte and Myelin Repair in Traumatic CNS Injury Front. Cell Neurosci. 2021 14 619707 10.3389/fncel.2020.619707 33505250 PMC7829188 · DOI
  111. [118]Duncan I.D. Radcliff A.B. Heidari M. Kidd G. August B.K. Wierenga L.A. The adult oligodendrocyte can participate in remyelination Proc. Natl. Acad. Sci. USA 2018 115 11807 11816 10.1073/pnas.1808064115 PMC6294923 30487224 · DOI · Paper page
  112. [119]Mezydlo A. Treiber N. Ullrich Gavilanes E.M. Eichenseer K. Ancău M. Wens A. Ares Carral C. Schifferer M. Snaidero N. Misgeld T. Remyelination by surviving oligodendrocytes is inefficient in the inflamed mammalian cortex Neuron 2023 111 1748 1759.e8 10.1016/j.neuron.2023.03.031 37071991 · DOI · Paper page
  113. [120]Gharagozloo M. Bannon R. Calabresi P.A. Breaking the barriers to remyelination in multiple sclerosis Curr. Opin. Pharmacol. 2022 63 102194 10.1016/j.coph.2022.102194 35255453 PMC8995341 · DOI
  114. [121]Tiane A. Schepers M. Rombaut B. Hupperts R. Prickaerts J. Hellings N. van den Hove D. Vanmierlo T. From OPC to Oligodendrocyte: An Epigenetic Journey Cells 2019 8 1236 10.3390/cells8101236 31614602 PMC6830107 · DOI
  115. [122]Emery B. Lu Q.R. Transcriptional and Epigenetic Regulation of Oligodendrocyte Development and Myelination in the Central Nervous System Cold Spring Harb. Perspect. Biol. 2015 7 020461 10.1101/cshperspect.a020461 26134004 PMC4563712 · DOI
  116. [123]Hernandez M. Casaccia P. Interplay between transcriptional control and chromatin regulation in the oligodendrocyte lineage GLIA 2015 63 1357 1375 10.1002/glia.22818 25970296 PMC4470782 · DOI
  117. [124]Ye F. Chen Y. Hoang T. Montgomery R.L. Zhao X.H. Bu H. Hu T. Taketo M.M. van Es J.H. Clevers H. HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the beta-catenin-TCF interaction Nat. Neurosci. 2009 12 829 838 10.1038/nn.2333 19503085 PMC2701973 · DOI · Paper page
  118. [125]Castro K. Casaccia P. Epigenetic modifications in brain and immune cells of multiple sclerosis patients Mult. Scler. 2018 24 69 74 10.1177/1352458517737389 29307300 PMC5761344 · DOI
  119. [126]John G.R. Shankar S.L. Shafit-Zagardo B. Massimi A. Lee S.C. Raine C.S. Brosnan C.F. Multiple sclerosis: Re-expression of a developmental pathway that restricts oligodendrocyte maturation Nat. Med. 2002 8 1115 1121 10.1038/nm781 12357247 · DOI
  120. [127]Allan K.C. Miller T.E. Morton A.R. Scavuzzo M.A. Elitt M.S. Clayton B.L.L. Hu L.R. Vrabic J.K. Olsen H.E. Factor D.C. Cellular Maturation of Oligodendrocytes is Governed by Transient Gene Melting bioRxiv 2022 10.1101/2022.11.17.516981 · DOI
  121. [128]Dai Z.M. Sun S. Wang C. Huang H. Hu X. Zhang Z. Lu Q.R. Qiu M. Stage-specific regulation of oligodendrocyte development by Wnt/β-catenin signaling J. Neurosci. 2014 34 8467 8473 10.1523/JNEUROSCI.0311-14.2014 24948802 PMC4147624 · DOI
  122. [129]Hammond E. Lang J. Maeda Y. Pleasure D. Angus-Hill M. Xu J. Horiuchi M. Deng W. Guo F. The Wnt effector transcription factor 7-like 2 positively regulates oligodendrocyte differentiation in a manner independent of Wnt/β-catenin signaling J. Neurosci. 2015 35 5007 5022 10.1523/JNEUROSCI.4787-14.2015 25810530 PMC6705374 · DOI
  123. [130]Yu Y. Casaccia P. Lu Q.R. Shaping the oligodendrocyte identity by epigenetic control Epigenetics 2010 5 124 128 10.4161/epi.5.2.11160 20160514 PMC2962897 · DOI
  124. [131]Juryńczyk M. Selmaj K. Notch: A new player in MS mechanisms J. Neuroimmunol. 2010 218 3 11 10.1016/j.jneuroim.2009.08.010 19748685 · DOI
  125. [132]Wu M. Hernandez M. Shen S. Sabo J.K. Kelkar D. Wang J. O’Leary R. Phillips G.R. Cate H.S. Casaccia P. Differential modulation of the oligodendrocyte transcriptome by sonic hedgehog and bone morphogenetic protein 4 via opposing effects on histone acetylation J. Neurosci. 2012 32 6651 6664 10.1523/JNEUROSCI.4876-11.2012 22573687 PMC3412138 · DOI
  126. [133]Haase S. Linker R.A. Inflammation in multiple sclerosis Ther. Adv. Neurol. Disord. 2021 14 17562864211007687 10.1177/17562864211007687 33948118 PMC8053832 · DOI
  127. [134]Itoh T. Horiuchi M. Itoh A. Interferon-triggered transcriptional cascades in the oligodendroglial lineage: A comparison of induction of MHC class II antigen between oligodendroglial progenitor cells and mature oligodendrocytes J. Neuroimmunol. 2009 212 53 64 10.1016/j.jneuroim.2009.04.021 19467717 PMC2710417 · DOI
  128. [135]Brambilla R. Ashbaugh J.J. Magliozzi R. Dellarole A. Karmally S. Szymkowski D.E. Bethea J.R. Inhibition of soluble tumour necrosis factor is therapeutic in experimental autoimmune encephalomyelitis and promotes axon preservation and remyelination Brain 2011 134 2736 2754 10.1093/brain/awr199 21908877 PMC3170538 · DOI
  129. [137]Horellou P. Wang M. Keo V. Chrétien P. Serguera C. Waters P. Deiva K. Increased interleukin-6 correlates with myelin oligodendrocyte glycoprotein antibodies in pediatric monophasic demyelinating diseases and multiple sclerosis J. Neuroimmunol. 2015 289 1 7 10.1016/j.jneuroim.2015.10.002 26616865 · DOI
  130. [138]Lang B.T. Cregg J.M. DePaul M.A. Tran A.P. Xu K. Dyck S.M. Madalena K.M. Brown B.P. Weng Y.L. Li S. Modulation of the proteoglycan receptor PTPσ promotes recovery after spinal cord injury Nature 2015 518 404 408 10.1038/nature13974 25470046 PMC4336236 · DOI · Paper page
  131. [139]Ghorbani S. Yong V.W. The extracellular matrix as modifier of neuroinflammation and remyelination in multiple sclerosis Brain 2021 144 1958 1973 10.1093/brain/awab059 33889940 PMC8370400 · DOI
  132. [140]Wei S.S. Chen L. Yang F.Y. Wang S.Q. Wang P. The role of fibronectin in multiple sclerosis and the effect of drug delivery across the blood-brain barrier Neural Regen. Res. 2023 18 2147 2155 10.4103/1673-5374.369102 37056122 PMC10328269 · DOI
  133. [142]Bauch J. Faissner A. The Extracellular Matrix Proteins Tenascin-C and Tenascin-R Retard Oligodendrocyte Precursor Maturation and Myelin Regeneration in a Cuprizone-Induced Long-Term Demyelination Animal Model Cells 2022 11 1773 10.3390/cells11111773 35681468 PMC9179356 · DOI
  134. [143]López-Muguruza E. Matute C. Alterations of Oligodendrocyte and Myelin Energy Metabolism in Multiple Sclerosis Int. J. Mol. Sci. 2023 24 12912 10.3390/ijms241612912 37629092 PMC10454078 · DOI
  135. [144]Gao R. Song S.J. Tian M.Y. Wang L.B. Zhang Y. Li X. Myelin debris phagocytosis in demyelinating disease GLIA 2024 72 1934 1954 10.1002/glia.24602 39073200 · DOI
  136. [145]Rosko L. Smith V.N. Yamazaki R. Huang J.K. Oligodendrocyte Bioenergetics in Health and Disease Neuroscientist 2019 25 334 343 10.1177/1073858418793077 30122106 PMC6745601 · DOI
  137. [146]Narine M. Colognato H. Current Insights Into Oligodendrocyte Metabolism and Its Power to Sculpt the Myelin Landscape Front. Cell Neurosci. 2022 16 892968 10.3389/fncel.2022.892968 35573837 PMC9097137 · DOI
  138. [147]Liu H. Wang S. Wang J. Guo X. Song Y. Fu K. Gao Z. Liu D. He W. Yang L.L. Energy metabolism in health and diseases Signal Transduct. Target. Ther. 2025 10 69 10.1038/s41392-025-02141-x 39966374 PMC11836267 · DOI
  139. [148]Bonora M. De Marchi E. Patergnani S. Suski J.M. Celsi F. Bononi A. Giorgi C. Marchi S. Rimessi A. Duszyński J. Tumor necrosis factor-α impairs oligodendroglial differentiation through a mitochondria-dependent process Cell Death Differ. 2014 21 1198 1208 10.1038/cdd.2014.35 24658399 PMC4085526 · DOI
  140. [149]Ziabreva I. Campbell G. Rist J. Zambonin J. Rorbach J. Wydro M.M. Lassmann H. Franklin R.J. Mahad D. Injury and differentiation following inhibition of mitochondrial respiratory chain complex IV in rat oligodendrocytes GLIA 2010 58 1827 1837 10.1002/glia.21052 20665559 PMC3580049 · DOI
  141. [150]Duncan G.J. Simkins T.J. Emery B. Neuron-Oligodendrocyte Interactions in the Structure and Integrity of Axons Front. Cell Dev. Biol. 2021 9 653101 10.3389/fcell.2021.653101 33763430 PMC7982542 · DOI
  142. [151]Spaas J. van Veggel L. Schepers M. Tiane A. van Horssen J. Wilson D.M. Moya P.R. Piccart E. Hellings N. Eijnde B.O. Oxidative stress and impaired oligodendrocyte precursor cell differentiation in neurological disorders Cell. Mol. Life Sci. 2021 78 4615 4637 10.1007/s00018-021-03802-0 33751149 PMC8195802 · DOI
  143. [152]Baud O. Haynes R.F. Wang H. Folkerth R.D. Li J. Volpe J.J. Rosenberg P.A. Developmental up-regulation of MnSOD in rat oligodendrocytes confers protection against oxidative injury Eur. J. Neurosci. 2004 20 29 40 10.1111/j.0953-816X.2004.03451.x 15245476 · DOI
  144. [153]Lipinski B. Hydroxyl radical and its scavengers in health and disease Oxid. Med. Cell Longev. 2011 2011 809696 10.1155/2011/809696 21904647 PMC3166784 · DOI
  145. [154]Nissanka N. Moraes C.T. Mitochondrial DNA damage and reactive oxygen species in neurodegenerative disease FEBS Lett. 2018 592 28 742 10.1002/1873-3468.12956 29281123 PMC6942696 · DOI
  146. [155]Xu X. Pang Y. Fan X. Mitochondria in oxidative stress, inflammation and aging: From mechanisms to therapeutic advances Signal Transduct. Target. Ther. 2025 10 190 10.1038/s41392-025-02253-4 40500258 PMC12159213 · DOI
  147. [156]Haider L. Fischer M.T. Frischer J.M. Bauer J. Höftberger R. Botond G. Esterbauer H. Binder C.J. Witztum J.L. Lassmann H. Oxidative damage in multiple sclerosis lesions Brain 2011 134 1914 1924 10.1093/brain/awr128 21653539 PMC3122372 · DOI
  148. [157]Campbell G. Mahad D.J. Mitochondrial dysfunction and axon degeneration in progressive multiple sclerosis FEBS Lett. 2018 592 1113 1121 10.1002/1873-3468.13013 29453889 · DOI
  149. [158]van den Berg R. Hoogenraad C.C. Hintzen R.Q. Axonal transport deficits in multiple sclerosis: Spiraling into the abyss Acta Neuropathol. 2017 134 1 14 10.1007/s00401-017-1697-7 28315956 PMC5486629 · DOI
  150. [159]Zhai D. Yan S. Samsom J. Wang L. Su P. Jiang A. Zhang H. Jia Z. Wallach I. Heifets A. Small-molecule targeting AMPA-mediated excitotoxicity has therapeutic effects in mouse models for multiple sclerosis Sci. Adv. 2023 9 6187 10.1126/sciadv.adj6187 PMC10708182 38064562 · DOI
  151. [160]Hill K.E. Zollinger L.V. Watt H.E. Carlson N.G. Rose J.W. Inducible nitric oxide synthase in chronic active multiple sclerosis plaques: Distribution, cellular expression and association with myelin damage J. Neuroimmunol. 2004 151 171 179 10.1016/j.jneuroim.2004.02.005 15145615 · DOI · Paper page
  152. [161]Li S. Lin W. Tchantchou F. Lai R. Wen J. Zhang Y. Protein kinase C mediates peroxynitrite toxicity to oligodendrocytes Mol. Cell. Neurosci. 2011 48 62 71 10.1016/j.mcn.2011.06.006 21708260 · DOI
  153. [165]Riekkinen P.J. Palo J. Arstila A.U. Savolainen H.J. Rinne U.K. Kivalo E.K. Frey H. Protein composition of multiple sclerosis myelin Arch. Neurol. 1971 24 545 549 10.1001/archneur.1971.00480360079010 5089900 · DOI
  154. [166]Raasakka A. Kursula P. Flexible Players within the Sheaths: The Intrinsically Disordered Proteins of Myelin in Health and Disease Cells 2020 9 470 10.3390/cells9020470 32085570 PMC7072810 · DOI
  155. [167]Chen Y. Kunjamma R.B. Weiner M. Chan J.R. Popko B. Prolonging the integrated stress response enhances CNS remyelination in an inflammatory environment eLife 2021 10 e65469 10.7554/elife.65469 33752802 PMC7987340 · DOI
  156. [168]Maghbooli Z. Sayahpour F.A. Varzandi T. Masoumi M.R. Sahraian M.A. The interplay between endoplasmic reticulum stress and inflammation in multiple sclerosis Sci. Rep. 2025 15 22916 10.1038/s41598-025-06996-6 40594452 PMC12217625 · DOI
  157. [169]Stone S. Lin W. The unfolded protein response in multiple sclerosis Front. Neurosci. 2015 9 264 10.3389/fnins.2015.00264 26283904 PMC4518158 · DOI
  158. [170]Lin W. Impaired eIF2B activity in ligodendrocytes contributes to VWMD pathogenesis Neural Regen. Res. 2015 10 195 197 10.4103/1673-5374.152366 25883611 PMC4392660 · DOI
  159. [171]Junjappa R.P. Patil P. Bhattarai K.R. Kim H.R. Chae H.J. IRE1α Implications in Endoplasmic Reticulum Stress-Mediated Development and Pathogenesis of Autoimmune Diseases Front. Immunol. 2018 9 1289 10.3389/fimmu.2018.01289 29928282 PMC5997832 · DOI
  160. [172]Stone S. Wu S. Jamison S. Durose W. Pallais J.P. Lin W. Activating transcription factor 6α deficiency exacerbates oligodendrocyte death and myelin damage in immune-mediated demyelinating diseases GLIA 2018 66 1331 1345 10.1002/glia.23307 29436030 PMC6019578 · DOI
  161. [173]Mháille A.N. McQuaid S. Windebank A. Cunnea P. McMahon J. Samali A. FitzGerald U. Increased expression of endoplasmic reticulum stress-related signaling pathway molecules in multiple sclerosis lesions J. Neuropathol. Exp. Neurol. 2008 67 200 211 10.1097/NEN.0b013e318165b239 18344911 · DOI · Paper page
  162. [174]Yoshida H. Matsui T. Yamamoto A. Okada T. Mori K. XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor Cell 2001 107 881 891 10.1016/S0092-8674(01)00611-0 11779464 · DOI
  163. [175]Lei Y. Yu H. Ding S. Liu H. Liu C. Fu R. Molecular mechanism of ATF6 in unfolded protein response and its role in disease Heliyon 2024 10 25937 10.1016/j.heliyon.2024.e25937 38434326 PMC10907738 · DOI
  164. [176]Lin W. Stone S. Unfolded protein response in myelin disorders Neural Regen. Res. 2020 15 636 645 10.4103/1673-5374.266903 31638085 PMC6975143 · DOI
  165. [177]Sharma G. Gopinath S. Lakshmi Narasimhan R. Exploring the Molecular Aspects of Glycosylation in MOG Antibody Disease (MOGAD) Curr. Protein Pept. Sci. 2022 23 384 394 10.2174/1389203723666220815110509 36285457 · DOI
  166. [178]Feigenson K. Reid M. See J. Crenshaw E.B. Grinspan J.B. Wnt signaling is sufficient to perturb oligodendrocyte maturation Mol. Cell. Neurosci. 2009 42 255 265 10.1016/j.mcn.2009.07.010 19619658 · DOI
  167. [179]Fancy S.P. Baranzini S.E. Zhao C. Yuk D.I. Irvine K.A. Kaing S. Sanai N. Franklin R.J. Rowitch D.H. Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS Genes. Dev. 2009 23 1571 1585 10.1101/gad.1806309 19515974 PMC2704469 · DOI
  168. [180]Shimizu T. Kagawa T. Wada T. Muroyama Y. Takada S. Ikenaka K. Wnt signaling controls the timing of oligodendrocyte development in the spinal cord Dev. Biol. 2005 282 397 410 10.1016/j.ydbio.2005.03.020 15950605 · DOI
  169. [181]Huang S.M. Mishina Y.M. Liu S. Cheung A. Stegmeier F. Michaud G.A. Charlat O. Wiellette E. Zhang Y. Wiessner S. Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling Nature 2009 461 614 620 10.1038/nature08356 19759537 · DOI
  170. [183]Chen J. Li J. Miao Z. Xu X. Liu C.F. XAV939, a small molecular inhibitor, provides neuroprotective effects on oligodentrocytes J. Neurosci. Res. 2014 92 1252 1258 10.1002/jnr.23415 24861203 · DOI
  171. [184]Shih Y. Ly P.T.T. Wang J. Pallen C.J. Glial and Neuronal Protein Tyrosine Phosphatase Alpha (PTPα) Regulate Oligodendrocyte Differentiation and Myelination J. Mol. Neurosci. 2017 62 329 343 10.1007/s12031-017-0941-x 28647856 · DOI
  172. [185]Li Y. Liu L. Ding X. Liu Y. Yang Q. Ren B. Interleukin-1β attenuates the proliferation and differentiation of oligodendrocyte precursor cells through regulation of the microRNA-202-3p/β-catenin/Gli1 axis Int. J. Mol. Med. 2020 46 1217 1224 10.3892/ijmm.2020.4648 32582975 · DOI
  173. [186]Zhang N. Zhang S. Liu X. Zuo Y.Y. Cui Y.G. Wang F. Zhang J.H. Chang Y.Z. Yu P. Oligodendrocyte-specific knockout of FPN1 affects CNS myelination defects and depression-like behavior in mice Free Radic. Biol. Med. 2025 238 370 386 10.1016/j.freeradbiomed.2025.06.055 40609802 · DOI
  174. [187]Russo M. Zahaf A. Kassoussi A. Sharif A. Faure H. Traiffort E. Ruat M. Sonic Hedgehog Is an Early Oligodendrocyte Marker During Remyelination Cells 2024 13 1808 10.3390/cells13211808 39513915 PMC11545011 · DOI
  175. [188]Cohen M. Kicheva A. Ribeiro A. Blassberg R. Page K.M. Barnes C.P. Briscoe J. Ptch1 and Gli regulate Shh signalling dynamics via multiple mechanisms Nat. Commun. 2015 6 6709 10.1038/ncomms7709 25833741 PMC4396374 · DOI
  176. [189]Prajapati A. Mehan S. Khan Z. Chhabra S. Das Gupta G. Purmorphamine, a Smo-Shh/Gli Activator, Promotes Sonic Hedgehog-Mediated Neurogenesis and Restores Behavioural and Neurochemical Deficits in Experimental Model of Multiple Sclerosis Neurochem. Res. 2024 49 1556 1576 10.1007/s11064-023-04082-9 38160216 · DOI
  177. [190]Namchaiw P. Wen H. Mayrhofer F. Chechneva O. Biswas S. Deng W. Temporal and partial inhibition of GLI1 in neural stem cells (NSCs) results in the early maturation of NSC derived oligodendrocytes in vitro Stem Cell Res. Ther. 2019 10 272 10.1186/s13287-019-1374-y 31455382 PMC6712625 · DOI
  178. [191]Porcu G. Serone E. De Nardis V. Di Giandomenico D. Lucisano G. Scardapane M. Poma A. Ragnini-Wilson A. Clobetasol and Halcinonide Act as Smoothened Agonists to Promote Myelin Gene Expression and RxRγ Receptor Activation PLoS ONE. 2015 10 0144550 10.1371/journal.pone.0144550 PMC4689554 26658258 · DOI
  179. [192]Yao X. Su T. Verkman A.S. Clobetasol promotes remyelination in a mouse model of neuromyelitis optica Acta Neuropathol. Commun. 2016 4 42 10.1186/s40478-016-0309-4 27117475 PMC4845317 · DOI
  180. [193]Wang S. Sdrulla A.D. diSibio G. Bush G. Nofziger D. Hicks C. Weinmaster G. Barres B.A. Notch receptor activation inhibits oligodendrocyte differentiation Neuron 1998 21 63 75 10.1016/S0896-6273(00)80515-2 9697852 · DOI
  181. [194]Zhang Y. Argaw A.T. Gurfein B.T. Zameer A. Snyder B.J. Ge C. Lu Q.R. Rowitch D.H. Raine C.S. Brosnan C.F. Notch1 signaling plays a role in regulating precursor differentiation during CNS remyelination Proc. Natl. Acad. Sci. USA 2009 106 19162 19167 10.1073/pnas.0902834106 19855010 PMC2776461 · DOI · Paper page
  182. [195]Hammond T.R. Gadea A. Dupree J. Kerninon C. Nait-Oumesmar B. Aguirre A. Gallo V. Astrocyte-derived endothelin-1 inhibits remyelination through notch activation Neuron 2014 81 588 602 10.1016/j.neuron.2013.11.015 24507193 PMC3935216 · DOI · Paper page
  183. [196]Brosnan C.F. John G.R. Revisiting Notch in remyelination of multiple sclerosis lesions J. Clin. Investig. 2009 119 10 13 10.1172/JCI37786 19104146 PMC2613471 · DOI
  184. [197]Wang C. Zhang C.J. Martin B.N. Bulek K. Kang Z. Zhao J. Bian G. Carman J.A. Gao J. Dongre A. IL-17 induced NOTCH1 activation in oligodendrocyte progenitor cells enhances proliferation and inflammatory gene expression Nat. Commun. 2017 8 15508 10.1038/ncomms15508 28561022 PMC5460031 · DOI
  185. [198]Jurynczyk M. Jurewicz A. Bielecki B. Raine C.S. Selmaj K. Inhibition of Notch signaling enhances tissue repair in an animal model of multiple sclerosis J. Neuroimmunol. 2005 170 3 10 10.1016/j.jneuroim.2005.10.013 16290267 · DOI
  186. [199]Fletcher J.L. Wood R.J. Nguyen J. Norman E.M.L. Jun C.M.K. Prawdiuk A.R. Biemond M. Nguyen H.T.H. Northfield S.E. Hughes R.A. Targeting TrkB with a Brain-Derived Neurotrophic Factor Mimetic Promotes Myelin Repair in the Brain J. Neurosci. 2018 38 7088 7099 10.1523/JNEUROSCI.0487-18.2018 29976621 PMC6596092 · DOI
  187. [200]Xiao J. Thirty years of BDNF study in central myelination: From biology to therapy J. Neurochem. 2023 167 321 336 10.1111/jnc.15968 37747083 · DOI
  188. [201]Makar T.K. Nimmagadda V.K. Singh I.S. Lam K. Mubariz F. Judge S.I. Trisler D. Bever C.T. Jr. TrkB agonist, 7,8-dihydroxyflavone, reduces the clinical and pathological severity of a murine model of multiple sclerosis J. Neuroimmunol. 2016 292 9 20 10.1016/j.jneuroim.2016.01.002 26943953 · DOI
  189. [202]Al-Samerria S. Radovick S. The Role of Insulin-like Growth Factor-1 (IGF-1) in the Control of Neuroendocrine Regulation of Growth Cells 2021 10 2664 10.3390/cells10102664 34685644 PMC8534318 · DOI
  190. [203]Zeger M. Popken G. Zhang J. Xuan S. Lu Q.R. Schwab M.H. Nave K.A. Rowitch D. D’Ercole A.J. Ye P. Insulin-like growth factor type 1 receptor signaling in the cells of oligodendrocyte lineage is required for normal in vivo oligodendrocyte development and myelination GLIA 2007 55 400 411 10.1002/glia.20469 17186502 PMC1774584 · DOI
  191. [204]Bibollet-Bahena O. Almazan G. IGF-1-stimulated protein synthesis in oligodendrocyte progenitors requires PI3K/mTOR/Akt and MEK/ERK pathways J. Neurochem. 2009 109 1440 1451 10.1111/j.1471-4159.2009.06071.x 19453943 · DOI
  192. [205]Yao D.L. Liu X. Hudson L.D. Webster H.D. Insulin-like growth factor I treatment reduces demyelination and up-regulates gene expression of myelin-related proteins in experimental autoimmune encephalomyelitis Proc. Natl. Acad. Sci. USA 1995 92 6190 6194 10.1073/pnas.92.13.6190 7541143 PMC41668 · DOI
  193. [206]Ye P. D’Ercole A.J. Insulin-like growth factor I protects oligodendrocytes from tumor necrosis factor-alpha-induced injury Endocrinology 1999 140 3063 3072 10.1210/endo.140.7.6754 10385398 · DOI
  194. [207]Hlavica M. Delparente A. Good A. Good N. Plattner P.S. Seyedsadr M.S. Schwab M.E. Figlewicz D.P. Ineichen B.V. Intrathecal insulin-like growth factor 1 but not insulin enhances myelin repair in young and aged rats Neurosci. Lett. 2017 648 41 46 10.1016/j.neulet.2017.03.047 28363754 · DOI · Paper page
  195. [208]Brinkmann B.G. Agarwal A. Sereda M.W. Garratt A.N. Müller T. Wende H. Stassart R.M. Nawaz S. Humml C. Velanac V. Neuregulin-1/ErbB signaling serves distinct functions in myelination of the peripheral and central nervous system Neuron 2008 59 581 595 18760695 PMC2628490
  196. [209]Galvez-Contreras A.Y. Quiñones-Hinojosa A. Gonzalez-Perez O. The role of EGFR and ErbB family related proteins in the oligodendrocyte specification in germinal niches of the adult mammalian brain Front. Cell Neurosci. 2013 7 258 10.3389/fncel.2013.00258 24381541 PMC3865447 · DOI
  197. [210]Mei L. Nave K.A. Neuregulin-ERBB signaling in the nervous system and neuropsychiatric diseases Neuron 2014 83 27 49 10.1016/j.neuron.2014.06.007 24991953 PMC4189115 · DOI
  198. [211]Xu C. Lv L. Zheng G. Li B. Gao L. Sun Y. Neuregulin1β1 protects oligodendrocyte progenitor cells from oxygen glucose deprivation injury induced apoptosis via ErbB4-dependent activation of PI3-kinase/Akt Brain Res. 2012 1467 104 112 10.1016/j.brainres.2012.05.044 22659027 · DOI
  199. [212]Kataria H. Alizadeh A. Shahriary G.M. Saboktakin Rizi S. Henrie R. Santhosh K.T. Thliveris J.A. Karimi-Abdolrezaee S. Neuregulin-1 promotes remyelination and fosters a pro-regenerative inflammatory response in focal demyelinating lesions of the spinal cord GLIA 2018 66 538 561 10.1002/glia.23264 29148104 · DOI
  200. [213]Gregath A. Lu Q.R. Epigenetic modifications-insight into oligodendrocyte lineage progression, regeneration, and disease FEBS Lett. 2018 592 1063 1078 10.1002/1873-3468.12999 29427507 PMC5903970 · DOI

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Authors
García-Domínguez, M.
Affiliations
Program of Immunology and Immunotherapy, CIMA-Universidad de Navarra, 31008 Pamplona, Spain
Venue
Cells
Publisher
MDPI AG
Published
2025-09-09
Volume
14
Issue
18
Pages
1408
ISSN
2073-4409 (ISSN-L)
DOI
10.3390/cells14181408
PMC
PMC12468040
OpenAlex
W4414156517
Cited by
13
References
271
Citations by year
2026: 10 · 2025: 3
FWCI
2.23
Type
journal article
Language
en
Open access
Licence
Locations
  • Cells (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
multiple sclerosis, oligodendrocytes, demyelination, remyelination, white matter, neurodegeneration, microglial activation, T cell cytotoxicity, oligodendrocyte precursor cells, oxidative stress, inflammatory cytokines, extracellular matrix, immune microenvironment, cell therapy, neuroprotection
MeSH terms
Remyelination, Animals, Humans, Multiple Sclerosis, Myelin Sheath, Oligodendroglia, White Matter

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