Regenerating CNS myelin — from mechanisms to experimental medicines
Open accessAbstract
Although the core concept of remyelination - based on the activation, migration, proliferation and differentiation of CNS progenitors - has not changed over the past 20 years, our understanding of the detailed mechanisms that underlie this process has developed considerably. We can now decorate the central events of remyelination with a host of pathways, molecules, mediators and cells, revealing a complex and precisely orchestrated process. These advances have led to recent drug-based and cell-based clinical trials for myelin diseases and have opened up hitherto unrecognized opportunities for drug-based approaches to therapeutically enhance remyelination.
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Efficient myelin debris removal and clearance by phagocytic cells are critical to eliminate inhibitory signals interfering with OPC activation, recruitment to the site of demyelination and/or differentiation into myelinating mature oligodendrocytes.
“Efficient myelin debris removal and clearance by phagocytic cells are critical to eliminate inhibitory signals interfering with OPC activation, recruitment to the site of demyelination and/or differentiation into myelinating mature OLs [14, 26, 27].”
From TREM2 activation on microglia promotes myelin debris clearance and remyelination in a model of multiple sclerosis (2020) · cites this paper as [14]
In “Systemic factors and remyelination” (page not available), the review says phagocytic macrophages clear myelin debris containing inhibitors of OPC differentiation, and that clearance prevents interference with the final stage of remyelination. It does not say that those debris-borne inhibitors interfere with OPC activation or recruitment; its discussion of macrophages during recruitment concerns a different role. (LLM, conf=0.88)
Experimental — accuracy not yet measuredCNS remyelination fails in prevalent neurodegenerative disorders, contributing to axon dysfunction/loss.
“Central nervous system (CNS) remyelination reinstates axon health/ function1, yet fails in prevalent neurodegenerative disorders contributing to axon dysfunction/loss for which there is an unmet therapeutic need.”
From Central nervous system regeneration is driven by microglia necroptosis and repopulation (2019) · cites this paper as [1]
The introductory passage (indexed under “Author biographies”; page unavailable) says remyelination ultimately fails for many patients with multiple sclerosis and that loss of myelin’s metabolic support is thought to contribute to axonal degeneration. “Why is remyelination important?” cautions that the observed association does not establish causality. The source does not establish remyelination failure across prevalent neurodegenerative disorders generally. (LLM, conf=0.88)
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IL4I1 augments CNS remyelination and axonal protection by modulating T cell driven inflammation
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Olesoxime accelerates myelination and promotes repair in models of demyelination
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Tamoxifen accelerates the repair of demyelinated lesions in the central nervous system
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Liver X receptors regulate cholesterol homeostasis in oligodendrocytes
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Self-citationOligodendrocyte progenitors: Adult stem cells of the central nervous system?
Crawford, A. H., Stockley, J. H., Tripathi, R. B., Richardson, W. D., & Franklin, R. J. M. (2014) · Experimental Neurology · doi:10.1016/j.expneurol.2014.04.027 · Cited by 79 · see citing works
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Activation of oligodendroglial Stat3 is required for efficient remyelination
Steelman, A. J., Zhou, Y., Koito, H., Kim, S., Payne, H. R., Lu, Q. R., & Li, J. (2016) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.03.023 · Cited by 68 · see citing works
Regenerative Capacity of Macrophages for Remyelination
Rawji, K. S., Mishra, M. K., & Yong, V. W. (2016) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2016.00047 · Cited by 67 · see citing works
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Self-citationTargeting human oligodendrocyte progenitors for myelin repair
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Efficient Remyelination Requires DNA Methylation
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Tocopherol Derivative TFA-12 Promotes Myelin Repair in Experimental Models of Multiple Sclerosis
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Stem cell-based therapy for human diseases
Hoang, D. M., Pham, P. T., Bach, T. Q., Ngo, A. T. L., Nguyen, Q. T., Phan, T. T. K., Nguyen, G. H., Le, P. T. T., Hoang, V. T., Forsyth, N. R., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01134-4 · Cited by 1,074 · see citing works
Multiple Sclerosis: Mechanisms and Immunotherapy
Baecher-Allan, C., Kaskow, B. J., & Weiner, H. L. (2018) · Neuron · doi:10.1016/j.neuron.2018.01.021 · Cited by 938 · see citing works
Myelin in the Central Nervous System: Structure, Function, and Pathology
Stadelmann, C., Timmler, S., Barrantes‐Freer, A., & Simons, M. (2019) · Physiological Reviews · doi:10.1152/physrev.00031.2018 · Cited by 735 · see citing works
“fails in these lesions, an issue that was reviewed in detail recently (191).”
BackgroundMultiple sclerosis progression: time for a new mechanism-driven framework
Kuhlmann, T., Moccia, M., Coetzee, T., Cohen, J. A., Correale, J., Graves, J., Marrie, R. A., Montalban, X., Yong, V. W., Thompson, A. J., et al. (2023) · The Lancet Neurology · doi:10.1016/s1474-4422(22)00289-7 · Cited by 667 · see citing works
Oligodendrocytes in development, myelin generation and beyond
Kuhn, S., Gritti, L., Crooks, D., & Dombrowski, Y. (2019) · Cells · doi:10.3390/cells8111424 · Cited by 625 · see citing works
“However, CNS remyelination can also be mediated by infiltrating Schwann cells, which was described for multiple conditions including MS and traumatic brain injury [2].”
BackgroundInfluentialMetformin restores CNS remyelination capacity by rejuvenating aged stem cells
Neumann, B., Baror, R., Zhao, C., Segel, M., Dietmann, S., Rawji, K. S., Foerster, S., McClain, C. R., Chalut, K., van Wijngaarden, P., et al. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2019.08.015 · Cited by 449 · see citing works
“The ability to regenerate oligodendrocytes, the myelin-forming cells of the CNS, contrasts with the poor capacity to regenerate neurons in most brain regions (Franklin and Ffrench-Constant, 2017).”
BackgroundSelf-citationTreg cell-derived osteopontin promotes microglia-mediated white matter repair after ischemic stroke
Shi, L., Sun, Z., Su, W., Xu, F., Xie, D., Zhang, Q. C., Dai, X., Iyer, K., Hitchens, T. K., Foley, L. M., et al. (2021) · Immunity · doi:10.1016/j.immuni.2021.04.022 · Cited by 430 · see citing works
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The pro-remyelination properties of microglia in the central nervous system
Lloyd, A. F., & Miron, V. E. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0184-2 · Cited by 381 · see citing works
Dynamics of oligodendrocyte generation in multiple sclerosis
Yeung, M. S. Y., Djelloul, M., Steiner, E., Bernard, S., Salehpour, M., Possnert, G., Brundin, L., & Frisén, J. (2019) · Nature · doi:10.1038/s41586-018-0842-3 · Cited by 376 · see citing works
Remyelination in multiple sclerosis: From basic science to clinical translation
Lubetzki, C., Zalc, B., Williams, A., Stadelmann, C., & Stankoff, B. (2020) · The Lancet Neurology · doi:10.1016/s1474-4422(20)30140-x · Cited by 350 · see citing works
Central nervous system regeneration is driven by microglia necroptosis and repopulation
Lloyd, A. F., Davies, C. L., Holloway, R. K., Labrak, Y., Ireland, G., Carradori, D., Dillenburg, A., Borger, E., Soong, D., Richardson, J. C., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0418-z · Cited by 316 · see citing works
Motor learning promotes remyelination via new and surviving oligodendrocytes
Bacmeister, C. M., Barr, H. J., McClain, C. R., Thornton, M. A., Nettles, D., Welle, C. G., & Hughes, E. G. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-0637-3 · Cited by 310 · see citing works
Molecular Control of Oligodendrocyte Development
Elbaz, B., & Popko, B. (2019) · Trends in Neurosciences · doi:10.1016/j.tins.2019.01.002 · Cited by 286 · see citing works
“In demyelinating diseases such as multiple sclerosis (MS), insufficient remyelination correlates with disease progression [9].”
BackgroundInfluentialCellular senescence and Alzheimer disease: the egg and the chicken scenario
Saez-Atienzar, S., & Masliah, E. (2020) · Nature Reviews Neuroscience · doi:10.1038/s41583-020-0325-z · Cited by 257 · see citing works
Graves, J. S., Krysko, K. M., Hua, L. H., Absinta, M., Franklin, R. J. M., & Segal, B. M. (2023) · The Lancet Neurology · doi:10.1016/s1474-4422(22)00184-3 · Cited by 260 · see citing works
Self-citationThe adult oligodendrocyte can participate in remyelination
Duncan, I. D., Radcliff, A. B., Heidari, M., Kidd, G., August, B. K., & Wierenga, L. A. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1808064115 · Cited by 259 · see citing works
“While studies of several models of remyelination have concluded that mature oligodendrocyte are incapable of remyelination (2), it is important to note that the two models presented here are different from the in vitro and in vivo models used previously to define the OPC as the primary, if not the sole, origin of remy…”
BackgroundAssociation between pathological and MRI findings in multiple sclerosis
Filippi, M., Brück, W., Chard, D., Fazekas, F., Geurts, J. J. G., Enzinger, C., Hametner, S., Kuhlmann, T., Preziosa, P., Rovira, À., et al. (2019) · The Lancet Neurology · doi:10.1016/s1474-4422(18)30451-4 · Cited by 252 · see citing works
Niu, J., Tsai, H., Hoi, K. K., Huang, N., Yu, G., Kim, K., Baranzini, S. E., Xiao, L., Chan, J. R., & Fancy, S. P. J. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0369-4 · Cited by 241 · see citing works
Multiple sclerosis: Neuroimmune crosstalk and therapeutic targeting
Charabati, M., Wheeler, M. A., Weiner, H. L., & Quintana, F. J. (2023) · Cell · doi:10.1016/j.cell.2023.03.008 · Cited by 229 · see citing works
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., et al. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03802-0 · Cited by 217 · see citing works
“Remyelination has been observed in a variety of traumatic and non-traumatic CNS disorders, aiming to protect denuded axons from degeneration and restore normal neuronal conduction [16, 18].”
BackgroundZhang, J., Buller, B., Zhang, Z. G., Zhang, Y., Lü, M., Rosene, D. L., Medalla, M., Moore, T. L., & Chopp, M. (2021) · Experimental Neurology · doi:10.1016/j.expneurol.2021.113895 · Cited by 195 · see citing works
Astrocytes and Microglia as Major Players of Myelin Production in Normal and Pathological Conditions
Traiffort, É., Kassoussi, A., Zahaf, A., & Laouarem, Y. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00079 · Cited by 189 · see citing works
“Activated OPCs finally express transcription factors such as TCF4 and Sox2, which serve to maintain OPC in the cell cycle and to prime these cells for further differentiation (Moyon et al., 2015; Franklin and Ffrench-Constant, 2017).”
BackgroundTREM2-dependent lipid droplet biogenesis in phagocytes is required for remyelination
Gouna, G., Klose, C., Bosch-Queralt, M., Liu, L., Gokce, O., Schifferer, M., Cantuti-Castelvetri, L., & Simons, M. (2021) · Journal of Experimental Medicine · doi:10.1084/jem.20210227 · Cited by 186 · see citing works
Astrocyte and Oligodendrocyte Cross-Talk in the Central Nervous System
Nutma, E., van Gent, D., Amor, S., & Peferoen, L. A. N. (2020) · Cells · doi:10.3390/cells9030600 · Cited by 184 · see citing works
Myelin: A gatekeeper of activity-dependent circuit plasticity?
Bonetto, G., Belin, D., & Káradóttir, R. T. (2021) · Science · doi:10.1126/science.aba6905 · Cited by 186 · see citing works
Astrocyte-oligodendrocyte interaction regulates central nervous system regeneration
Molina-Gonzalez, I., Holloway, R. K., Jiwaji, Z., Dando, O., Kent, S. A., Emelianova, K., Lloyd, A. F., Forbes, L. H., Mahmood, A., Skripuletz, T., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-39046-8 · Cited by 176 · see citing works
“Damage to myelin in the central nervous system (CNS) leads to loss of neuronal axon health and function in various neurological conditions (e.g. multiple sclerosis, spinal cord injury), which can be restored bytheregenerationofmyelin,termedremyelination 1 .”
Galectin-3, a rising star in modulating microglia activation under conditions of neurodegeneration
García-Revilla, J., Boza-Serrano, A., Espinosa-Oliva, A. M., Soto, M. S., Deierborg, T., Ruiz, R., de Pablos, R. M., Burguillos, M. A., & Venero, J. L. (2022) · Cell Death & Disease · doi:10.1038/s41419-022-05058-3 · Cited by 156 · see citing works
“In fact, oligodendroglial injury triggers demyelination, which is followed by a remyelination process that forms a new myelin sheet [103, 104].”
BackgroundNeurodegeneration in multiple sclerosis
Mey, G. M., Mahajan, K. R., & DeSilva, T. M. (2022) · WIREs Mechanisms of Disease · doi:10.1002/wsbm.1583 · Cited by 174 · see citing works
CNS remyelination and inflammation: From basic mechanisms to therapeutic opportunities
Franklin, R. J. M., & Simons, M. (2022) · Neuron · doi:10.1016/j.neuron.2022.09.023 · Cited by 184 · see citing works
Self-citationMicroglia regulation of central nervous system myelin health and regeneration
Kent, S. A., & Miron, V. E. (2024) · Nature Reviews Immunology · doi:10.1038/s41577-023-00907-4 · Cited by 183 · see citing works
“This process re-establishes neuronal function, improves neuronal stress responses and is neuroprotective 16 .”
Aging and Neurodegenerative Disease: Is the Adaptive Immune System a Friend or Foe?
Mayne, K., White, J. A., McMurran, C. E., Rivera, F. J., & de la Fuente, A. G. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.572090 · Cited by 167 · see citing works
“Regeneration in MS is centered on the differentiation of oligodendrocyte progenitor cells (OPC) into oligodendrocytes, which replace myelin sheaths to prevent axon degeneration in a process known as remyelination (Smith et al., 1979; Franklin and Ffrench-Constant, 2017).”
BackgroundCNS myelination and remyelination depend on fatty acid synthesis by oligodendrocytes
Dimas, P., Montani, L., Pereira, J. A., Moreno, D., Trötzmüller, M., Gerber, J., Semenkovich, C. F., Köfeler, H. C., & Suter, U. (2019) · eLife · doi:10.7554/elife.44702 · Cited by 178 · see citing works
“At this time point, focal lesions approach their full remyelination potential (Crawford et al., 2016; Franklin and Ffrench-Constant, 2017).”
BackgroundInfluentialPromoting remyelination in multiple sclerosis
Cunniffe, N., & Coles, A. (2019) · Journal of Neurology · doi:10.1007/s00415-019-09421-x · Cited by 142 · see citing works
Cunha, M. I., Su, M., Cantuti-Castelvetri, L., Müller, S. A., Schifferer, M., Djannatian, M., Alexopoulos, I., van der Meer, F., Winkler, A., van Ham, T. J., et al. (2020) · Journal of Experimental Medicine · doi:10.1084/jem.20191390 · Cited by 160 · see citing works
Revisiting remyelination: Towards a consensus on the regeneration of CNS myelin
Franklin, R. J. M., Frisén, J., & Lyons, D. A. (2021) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2020.09.009 · Cited by 154 · see citing works
Self-citationZhang, Q., Zhu, W., Xu, F., Dai, X., Shi, L., Cai, W., Mu, H., Hitchens, T. K., Foley, L. M., Liu, X., et al. (2019) · PLOS Biology · doi:10.1371/journal.pbio.3000330 · Cited by 160 · see citing works
Rawji, K. S., Young, A. M. H., Ghosh, T., Michaels, N. J., Mirzaei, R., Kappen, J., Kolehmainen, K. L., Alaeiilkhchi, N., Lozinski, B., Mishra, M. K., et al. (2020) · Acta Neuropathologica · doi:10.1007/s00401-020-02129-7 · Cited by 153 · see citing works
Self-citationA Vessel for Change: Endothelial Dysfunction in Cerebral Small Vessel Disease
Quick, S., Moss, J., Rajani, R. M., & Williams, A. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.11.003 · Cited by 146 · see citing works
“correlating with white matter hyperintensities seen by MRI scans of patients [127], and myelin loss both reduces axon conduction velocities and leaves axons vulnerable to degradation and damage (reviewed in [128]).”
BackgroundRobust Myelination of Regenerated Axons Induced by Combined Manipulations of GPR17 and Microglia
Wang, J., He, X., Meng, H., Li, Y., Dmitriev, P., Tian, F., Page, J. C., Lu, Q. R., & He, Z. (2020) · Neuron · doi:10.1016/j.neuron.2020.09.016 · Cited by 139 · see citing works
“As neuroinflammation has been shown to regulate OPC proliferation and differentiation (Franklin and Ffrench-Constant, 2017; Lassmann et al., 2018; Lloyd and Miron, 2019), we further examined the role of microglia in injured optic nerves on OPC proliferation and differentiation.”
BackgroundLesion stage-dependent causes for impaired remyelination in MS
Heß, K., Starost, L. J., Kieran, N. W., Thomas, C., Vincenten, M. C. J., Antel, J. P., Martino, G., Huitinga, I., Healy, L. M., & Kuhlmann, T. (2020) · Acta Neuropathologica · doi:10.1007/s00401-020-02189-9 · Cited by 137 · see citing works
TNF Production and Release from Microglia via Extracellular Vesicles: Impact on Brain Functions
Raffaele, S., Lombardi, M., Verderio, C., & Fumagalli, M. (2020) · Cells · doi:10.3390/cells9102145 · Cited by 140 · see citing works
Neuronal activity in vivo enhances functional myelin repair
Ortíz, F. C., Habermacher, C., Graciarena, M., Houry, P.-Y., Nishiyama, A., Nait‐Oumesmar, B., & Angulo, M. C. (2019) · JCI Insight · doi:10.1172/jci.insight.123434 · Cited by 133 · see citing works
“functional recovery of patients with long-standing and progressive disease (1).”
BackgroundInfluentialShen, K., Reichelt, M., Kyauk, R. V., Ngu, H., Shen, Y.-A. A., Foreman, O., Modrusan, Z., Friedman, B. A., Sheng, M., & Yuen, T. J. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.108835 · Cited by 138 · see citing works
Neuron-Oligodendrocyte Interactions in the Structure and Integrity of Axons
Duncan, G. J., Simkins, T., & Emery, B. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.653101 · Cited by 121 · see citing works
“Consequently, remyelination strategies are being pursued in diseases such as multiple sclerosis (MS) with the hope of not only recovering nerve conduction in the short term but also protecting axons against degeneration in the long term (Franklin et al., 2012; Franklin and Ffrench-Constant, 2017; Lubetzki et al., 2020…”
BackgroundMultiple sclerosis: molecular pathogenesis and therapeutic intervention
Boutitah-Benyaich, I., Eixarch, H., Villacieros‐Álvarez, J., Hervera, A., Cobo‐Calvo, Á., Montalbán, X., & Espejo, C. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02415-4 · Cited by 136 · see citing works
Neely, S. A., Williamson, J. M., Klingseisen, A., Zoupi, L., Early, J. J., Williams, A., & Lyons, D. A. (2022) · Nature Neuroscience · doi:10.1038/s41593-021-01009-x · Cited by 132 · see citing works
The neural stem cell secretome and its role in brain repair
Willis, C. M., Nicaise, A. M., Peruzzotti‐Jametti, L., & Pluchino, S. (2019) · Brain Research · doi:10.1016/j.brainres.2019.146615 · Cited by 117 · see citing works
“neurorestorative cues to initiate regeneration of the damaged tissue (Franklin and Ffrench-Constant, 2008; Franklin and Ffrench-Constant, 2017).”
BackgroundRemyelination and ageing: Reversing the ravages of time
Neumann, B., Segel, M., Chalut, K. J., & Franklin, R. J. M. (2019) · Multiple Sclerosis Journal · doi:10.1177/1352458519884006 · Cited by 113 · see citing works
Self-citationSun, Z., Gao, C., Gao, D., Sun, R., Li, W., Wang, F., Wang, Y., Cao, H., Zhou, G., Zhang, J., et al. (2021) · Fluids and Barriers of the CNS · doi:10.1186/s12987-021-00255-2 · Cited by 115 · see citing works
“The myelin sheath is formed by mature myelin-producing oligodendrocytes, and WM damage is caused by the loss of mature myelin-producing oligodendrocytes [36].”
BackgroundOligodendrocytes and Microglia: Key Players in Myelin Development, Damage and Repair
Kalafatakis, I., & Karagogeos, D. (2021) · Biomolecules · doi:10.3390/biom11071058 · Cited by 111 · see citing works
“Why then, is repair after CNS insult not sustained, as evidenced by the majority of MS lesions being of the chronic demyelinating type [27]? The reasons for remyelination failure are not well understood [28].”
BackgroundThe Molecular Basis for Remyelination Failure in Multiple Sclerosis
Gruchot, J., Weyers, V., Göttle, P., Förster, M., Hartung, H., Küry, P., & Kremer, D. (2019) · Cells · doi:10.3390/cells8080825 · Cited by 109 · see citing works
“Interestingly, differences in the extent of myelin regeneration can be observed between individual lesions and patients, potentially indicating heterogeneity within the OPC population and the mechanisms underlying failing myelin repair in any given patient [8].”
BackgroundRaffaele, S., Gelosa, P., Bonfanti, E., Lombardi, M., Castiglioni, L., Cimino, M., Sironi, L., Abbracchio, M. P., Verderio, C., & Fumagalli, M. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2020.12.009 · Cited by 106 · see citing works
“Upon a demyelinating injury, the oligodendrocyte precursor cells (OPCs) present in the adult brain parenchyma migrate to the lesion site, proliferate, and differentiate to myelinating oligodendrocytes.(10,11) Specifically, fate-mapping studies using the conditional reporter mouse line GPR17-iCreER:CAG-enhanced green f…”
BackgroundDiversity in the oligodendrocyte lineage: Plasticity or heterogeneity?
Foerster, S., Hill, M. F. E., & Franklin, R. J. M. (2019) · Glia · doi:10.1002/glia.23607 · Cited by 103 · see citing works
Self-citationOligodendrocyte-encoded Kir4.1 function is required for axonal integrity
Schirmer, L., Möbius, W., Zhao, C., Cruz-Herranz, A., Haim, L. B., Cordano, C., Shiow, L. R., Kelley, K. W., Sadowski, B., Timmons, G. M., et al. (2018) · eLife · doi:10.7554/elife.36428 · Cited by 100 · see citing works
“1 during acute and chronic remyelination after focal white matter 196 injury, we utilized the lysolecithin glial toxic injury model in the spinal cord at P80 (45-47).”
MethodInfluentialSelf-citationBrown, J. W. L., Cunniffe, N. G., Prados, F., Kanber, B., Jones, J., Needham, E., Georgieva, Z. G., Rog, D. J., Pearson, O. R., Overell, J. R., et al. (2021) · The Lancet Neurology · doi:10.1016/s1474-4422(21)00179-4 · Cited by 101 · see citing works
Self-citationChanges in the Oligodendrocyte Progenitor Cell Proteome with Ageing
de la Fuente, A. G., Queiroz, R. M. L., Ghosh, T., McMurran, C. E., Cubillos, J. F., Bergles, D. E., Fitzgerald, D. C., Jones, C. A., Lilley, K. S., Glover, C. P. J., et al. (2020) · Molecular & Cellular Proteomics · doi:10.1074/mcp.ra120.002102 · Cited by 99 · see citing works
“three ages were selected for the following reasons: (1) devel-”
BackgroundSelf-citationGlial cell alterations in diabetes-induced neurodegeneration
Llorián‐Salvador, M., Cabeza‐Fernández, S., Gomez-Sanchez, J. A., & de la Fuente, A. G. (2024) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-023-05024-y · Cited by 100 · see citing works
“Myelin loss is generally rapidly restored through a process known as remyelination, a regenerative process by which OPCs respond to myelin damage differentiating into myelinating oligodendrocytes and restabilizing myelin around denuded CNS axons [106].”
BackgroundOligodendrocyte progenitor cells in Alzheimer's disease: from physiology to pathology
Zou, P., Wu, C., Liu, T. C.-Y., Duan, R., & Yang, L. (2023) · Translational Neurodegeneration · doi:10.1186/s40035-023-00385-7 · Cited by 97 · see citing works
“However, the nOPCs generate new oligodendrocytes for myelination, and the aOPCs generate that for remyelination [59, 60].”
BackgroundEpigenomic priming of immune genes implicates oligodendroglia in multiple sclerosis susceptibility
Meijer, M., Agirre, E., Kabbe, M., van Tuijn, C. A., Heskol, A., Zheng, C., Mendanha Falcão, A., Bartosovic, M., Kirby, L., Calini, D., et al. (2022) · Neuron · doi:10.1016/j.neuron.2021.12.034 · Cited by 98 · see citing works
“Oligodendrocyte precursor cells (OPCs) in the adult CNS are recruited to MS lesions and are thought to contribute to remyelination during disease remission (Franklin and Ffrench-Constant, 2017), although this capacity is hindered upon disease progression (Jäkel et al., 2019; Yeung et al., 2019).”
BackgroundInsights into myelin dysfunction in schizophrenia and bipolar disorder
Valdés‐Tovar, M., Rodríguez‐Ramírez, A. M., Rodríguez-Cárdenas, L., Sotelo-Ramírez, C. E., Camarena, B., Sanabrais‐Jiménez, M. A., Solís‐Chagoyán, H., Argueta, J., & López-Riquelme, G. O. (2022) · World Journal of Psychiatry · doi:10.5498/wjp.v12.i2.264 · Cited by 93 · see citing works
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“In contrast to typical chemical demyelination models which have a single wave of OPC proliferation, differentiation and typically complete remyelination (Blakemore & Franklin, 2008; Franklin & ffrench-Constant, 2017), OPC proliferation and new oligodendrocyte formation continue for weeks after SCI.”
ResultLipids in regulating oligodendrocyte structure and function
Montani, L. (2020) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2020.07.016 · Cited by 94 · see citing works
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White matter microglia heterogeneity in the CNS
Amor, S., McNamara, N. B., Gerrits, E., Marzin, M. C., Kooistra, S. M., Miron, V. E., & Nutma, E. (2022) · Acta Neuropathologica · doi:10.1007/s00401-021-02389-x · Cited by 89 · see citing works
Myelination-independent functions of oligodendrocyte precursor cells in health and disease
Xiao, Y. C., & Czopka, T. (2023) · Nature Neuroscience · doi:10.1038/s41593-023-01423-3 · Cited by 92 · see citing works
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“Once differentiated, mature oligodendrocytes will engage with demyelinated axons and re-ensheath these axons with myelin to restore neurological function and neuroprotection 58 .”
Qian, Z., Li, H., Yang, H., Yang, Q., Lu, Z., Wang, L., Chen, Y., & Li, X. (2021) · Science Advances · doi:10.1126/sciadv.abi5811 · Cited by 91 · see citing works
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“However, it is now clear that OPCs and neural stem cells present in the CNS throughout life can generate new oligodendrocytes following damage to myelin, and that these cells can in turn regenerate myelin through the process of remyelination (Franklin and ffrench-Constant, 2017; Prineas and Connell, 1979; Samanta et a…”
BackgroundInfluentialHou, J., Zhou, Y., Cai, Z., Terekhova, M., Swain, A., Andhey, P. S., Guimaraes, R. M., Ulezko Antonova, A., Qiu, T., Sviben, S., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112293 · Cited by 85 · see citing works
Diet-dependent regulation of TGFβ impairs reparative innate immune responses after demyelination
Bosch-Queralt, M., Cantuti-Castelvetri, L., Damkou, A., Schifferer, M., Schlepckow, K., Alexopoulos, I., Lütjohann, D., Klose, C., Vaculčiaková, L., Masuda, T., et al. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00341-7 · Cited by 88 · see citing works
Naturally Occurring Nervonic Acid Ester Improves Myelin Synthesis by Human Oligodendrocytes
Lewkowicz, N., Piątek, P., Namiecińska, M., Domowicz, M., Bonikowski, R., Szemraj, J., Przygodzka, P., Stasiołek, M., & Lewkowicz, P. (2019) · Cells · doi:10.3390/cells8080786 · Cited by 83 · see citing works
“During the physiological reconstitution of CNS, OPCs, being abundant throughout the gray matter of CNS, migrate toward demyelinating plaque, where they can generate new OLs [29].”
BackgroundMyelin plasticity in adulthood and aging
Chapman, T. W., & Hill, R. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.134645 · Cited by 85 · see citing works
“Chronic stages of multiple sclerosis are characterized by incomplete remyelination [104] presumably due to the inability of NG2 glia to differentiate [99].”
BackgroundOsorio-Querejeta, I., Carregal‐Romero, S., Ayerdi-Izquierdo, A., Mäger, I., Nash, L. A., Wood, M. J. A., Egimendia, A., Betanzos, M., Alberro, A., Iparraguirre, L., et al. (2020) · Pharmaceutics · doi:10.3390/pharmaceutics12020186 · Cited by 82 · see citing works
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“These harmful events trigger a spontaneous repair process, known as remyelination, during which the oligodendrocyte precursor cells (OPCs), that persist in a quiescent state within the adult CNS [4,5], are activated, migrate, and differentiate to replace the OLs lost during pathological conditions [6].”
BackgroundCalcium Signaling in the Oligodendrocyte Lineage: Regulators and Consequences
Paez, P. M., & Lyons, D. A. (2020) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-100719-093305 · Cited by 82 · see citing works
“Numerous studies have indicated that the mechanisms that drive normal oligodendrocyte lineage progression through myelination are often essential for the regeneration of myelin (remyelination) following its loss or damage in disease or injury (Franklin & ffrench-Constant 2017).”
BackgroundInfluentialCentral Nervous System Remyelination: Roles of Glia and Innate Immune Cells
Baaklini, C. S., Rawji, K. S., Duncan, G. J., Ho, M. F. S., & Plemel, J. R. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00225 · Cited by 80 · see citing works
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The Role of Astrocytes in Remyelination
Rawji, K. S., Martinez, G. A. G., Sharma, A., & Franklin, R. J. M. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.05.006 · Cited by 78 · see citing works
Self-citationPu, H., Zheng, X., Jiang, X., Mu, H., Xu, F., Zhu, W., Ye, Q., Jizhang, Y., Hitchens, T. K., Shi, Y., et al. (2020) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x20941393 · Cited by 77 · see citing works
“The regeneration of myelin-forming OLs and the remyelination of functional axons are essential steps for the restoration of white matter integrity.(43) In addition to its well-known anti-inflammatory effects, our previous study identified a new function of IL-4 in the direct stimulation of OPC differentiation into mat…”
BackgroundMechanisms of axonal support by oligodendrocyte-derived extracellular vesicles
Krämer‐Albers, E., & Werner, H. B. (2023) · Nature reviews. Neuroscience · doi:10.1038/s41583-023-00711-y · Cited by 78 · see citing works
Galectin-3-Mediated Glial Crosstalk Drives Oligodendrocyte Differentiation and (Re)myelination
Thomas, L., & Pasquini, L. A. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00297 · Cited by 76 · see citing works
Astrocytes in myelination and remyelination
Molina-González, I., & Miron, V. E. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.134532 · Cited by 76 · see citing works
Hamaguchi, M., Muramatsu, R., Fujimura, H., Mochizuki, H., Kataoka, H., & Yamashita, T. (2019) · eLife · doi:10.7554/elife.41869 · Cited by 73 · see citing works
“Successful remyelination requires OPC proliferation, migration, differentiation to oligodendrocytes, and finally, maturation into myelinating oligodendrocytes (Franklin and Ffrench-Constant, 2017).”
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“Together with therapies targeting primary causes of demyelination, many research efforts have focused on promoting the regenerative potential of myelinating glia and their progenitors (Plemel et al., 2017; Stangel et al., 2017; Franklin and ffrench-Constant, 2017).”
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Remyelination by surviving oligodendrocytes is inefficient in the inflamed mammalian cortex
Mezydlo, A., Treiber, N., Ullrich Gavilanes, E. M., Eichenseer, K., Ancău, M., Wens, A., Ares Carral, C., Schifferer, M., Snaidero, N., Misgeld, T., et al. (2023) · Neuron · doi:10.1016/j.neuron.2023.03.031 · Cited by 63 · see citing works
Strategies for Oligodendrocyte and Myelin Repair in Traumatic CNS Injury
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Oligodendrocyte precursor cells as a therapeutic target for demyelinating diseases
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Microglia Diversity in Health and Multiple Sclerosis
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Oligodendrocyte Differentiation and Myelination Is Potentiated via GABAB Receptor Activation
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Scaffold-Mediated Sustained, Non-viral Delivery of miR-219/miR-338 Promotes CNS Remyelination
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“27 No 2 Februar in axons cannot occur, which in turn results in perturbed axonal transport, degeneration, and ultimately functional impairment.(4) The importance of this structure was further displayed in patients with non-penetrating traumatic nerve injuries in the CNS, where even though a portion of axons was spared…”
BackgroundSelf-citationAndrovic, P., Schifferer, M., Perez Anderson, K., Cantuti-Castelvetri, L., Jiang, H., Ji, H., Liu, L., Gouna, G., Berghoff, S. A., Besson-Girard, S., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-39447-9 · Cited by 67 · see citing works
Chen, C. Z.-Y., Neumann, B., Förster, S., & Franklin, R. J. M. (2021) · Open Biology · doi:10.1098/rsob.200352 · Cited by 66 · see citing works
“Remyelination of central axons reverses conduction deficits and protects axons from secondary degeneration [5]; however, whether oligodendrocyte- or SC-mediated remyelination can achieve this to equal degrees is not known.”
BackgroundSelf-citationWang, X., Chang, L., Wan, X., Tan, Y., Qu, Y., Shan, J., Yang, Y. H., Ma, L., & Hashimoto, K. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105635 · Cited by 66 · see citing works
“After CPZ withdrawal, spontaneous remyelination was shown in CPZ-treated mice (Franklin and Ffrench-Constant, 2017; Torkildsen et al., 2008).”
Background
- Authors
- Franklin, R. J. M., & ffrench-Constant, C.
- Affiliations
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- Corresponding author
- Franklin, Robin J. M.
- Venue
- Nature Reviews Neuroscience
- Published
- 2017-11-16
- Volume
- 18
- Issue
- 12
- Pages
- 753-769
- ISSN
- 1471-003X (ISSN-L)
- 1471-0048
- OpenAlex
- W2770653478
- Semantic Scholar
- 873fe364632a01af9b64b05352afae59ba7235e0
- Cited by
- 647
- References
- 222
- Citations by year
- 2026: 84 · 2025: 72 · 2024: 84 · 2023: 58 · 2022: 83 · 2021: 83 · 2020: 70 · 2019: 79 · 2018: 33 · 2017: 1
- FWCI
- 7.99
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- Wellcome Trust (104783/Z/14/Z)
- Medical Research Council (MC_PC_12009)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- remyelination, central nervous system myelin, multiple sclerosis, demyelination, oligodendrocyte precursor cells, cell therapy, myelin diseases
- MeSH terms
- Animals, Cell Differentiation, Central Nervous System, Demyelinating Diseases, Humans, Myelin Sheath, Nerve Regeneration, Oligodendroglia
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