myelin sheath


Summary: The lipid-rich sheath surrounding AXONS in both the CENTRAL NERVOUS SYSTEMS and PERIPHERAL NERVOUS SYSTEM. The myelin sheath is an electrical insulator and allows faster and more energetically efficient conduction of impulses. The sheath is formed by the cell membranes of glial cells (SCHWANN CELLS in the peripheral and OLIGODENDROGLIA in the central nervous system). Deterioration of the sheath in DEMYELINATING DISEASES is a serious clinical problem.

Top Publications

  1. Deshmukh V, Tardif V, Lyssiotis C, Green C, Kerman B, Kim H, et al. A regenerative approach to the treatment of multiple sclerosis. Nature. 2013;502:327-332 pubmed publisher
    ..These studies should facilitate the development of effective new therapies for the treatment of multiple sclerosis that complement established immunosuppressive approaches. ..
  2. Gibson E, Purger D, Mount C, Goldstein A, Lin G, Wood L, et al. Neuronal activity promotes oligodendrogenesis and adaptive myelination in the mammalian brain. Science. 2014;344:1252304 pubmed publisher
    ..Oligodendrogenesis and myelination appear necessary for the observed functional improvement, as epigenetic blockade of oligodendrocyte differentiation and myelin changes prevents the activity-regulated behavioral improvement. ..
  3. Lundgaard I, Luzhynskaya A, Stockley J, Wang Z, Evans K, Swire M, et al. Neuregulin and BDNF induce a switch to NMDA receptor-dependent myelination by oligodendrocytes. PLoS Biol. 2013;11:e1001743 pubmed publisher
    ..These data resolve controversies over the signalling regulating myelination and suggest novel roles for neuregulin in schizophrenia and in remyelination after white matter damage. ..
  4. Glenn T, Talbot W. Signals regulating myelination in peripheral nerves and the Schwann cell response to injury. Curr Opin Neurobiol. 2013;23:1041-8 pubmed publisher
    ..In addition to forming the myelin sheath, Schwann cells orchestrate much of the regenerative response that occurs after injury to peripheral nerves...
  5. Czopka T, Ffrench Constant C, Lyons D. Individual oligodendrocytes have only a few hours in which to generate new myelin sheaths in vivo. Dev Cell. 2013;25:599-609 pubmed publisher
    ..It remains unknown when, during their life, individual oligodendrocytes can regulate myelin sheath number in vivo...
  6. Susuki K, Chang K, Zollinger D, Liu Y, Ogawa Y, Eshed Eisenbach Y, et al. Three mechanisms assemble central nervous system nodes of Ranvier. Neuron. 2013;78:469-82 pubmed publisher
    ..Our results demonstrate that ECM, paranodal, and axonal cytoskeletal mechanisms ensure robust CNS nodal Na? channel clustering. ..
  7. Brosius Lutz A, Barres B. Contrasting the glial response to axon injury in the central and peripheral nervous systems. Dev Cell. 2014;28:7-17 pubmed publisher
    ..This Review presents a comparison of the glial response to injury between the CNS and PNS and highlights features of the PNS glial response that, with continued study, might reveal long-sought-after keys to achieving CNS repair. ..
  8. HARLOW D, Macklin W. Inhibitors of myelination: ECM changes, CSPGs and PTPs. Exp Neurol. 2014;251:39-46 pubmed publisher
    ..Experimental Neurology (2013) vol. 247, pp. 113-121), highlights the need to better understand the ECM changes that accompany demyelination and their influence on oligodendrocytes and effective remyelination. ..
  9. Qiao G, Qian Z, Sun H, Xu W, Yan Z, Liu Y, et al. Remodeling of hyperpolarization-activated current, Ih, in Ah-type visceral ganglion neurons following ovariectomy in adult rats. PLoS ONE. 2013;8:e71184 pubmed publisher
    ..In conclusion, Ih plays a significant role in modulating the excitability of myelinated Ah-type VGNs in adult female rats. ..

More Information


  1. Simons M, Lyons D. Axonal selection and myelin sheath generation in the central nervous system. Curr Opin Cell Biol. 2013;25:512-9 pubmed publisher
    ..advances in identifying biophysical and signalling based mechanisms that are involved in axonal selection and myelin sheath generation by oligodendrocytes...
  2. Bercury K, Dai J, Sachs H, Ahrendsen J, Wood T, Macklin W. Conditional ablation of raptor or rictor has differential impact on oligodendrocyte differentiation and CNS myelination. J Neurosci. 2014;34:4466-80 pubmed publisher
    ..Also, we show that loss of Raptor in oligodendrocytes results in differential dysmyelination in specific areas of the CNS, with the greatest impact on spinal cord myelination. ..
  3. Noseda R, Belin S, Piguet F, Vaccari I, Scarlino S, Brambilla P, et al. DDIT4/REDD1/RTP801 is a novel negative regulator of Schwann cell myelination. J Neurosci. 2013;33:15295-305 pubmed publisher
    ..Moreover, loss of DDIT4 expression both in vitro and in vivo in Ddit4-null mice provokes sustained hypermyelination and enhanced mTORC1 activation, thus suggesting that this molecule is a novel negative regulator of PNS myelination. ..
  4. Kim W, Hsiao J, Bhatia S, Glaros E, Don A, Tsuruoka S, et al. ABCA8 stimulates sphingomyelin production in oligodendrocytes. Biochem J. 2013;452:401-10 pubmed publisher
  5. Xiao J, Ferner A, Wong A, Denham M, Kilpatrick T, Murray S. Extracellular signal-regulated kinase 1/2 signaling promotes oligodendrocyte myelination in vitro. J Neurochem. 2012;122:1167-80 pubmed publisher
    ..Collectively, these data identify that Erk1/2 signaling within oligodendrocytes exerts an important and direct effect to promote myelination. ..
  6. Beirowski B, Gustin J, Armour S, Yamamoto H, Viader A, North B, et al. Sir-two-homolog 2 (Sirt2) modulates peripheral myelination through polarity protein Par-3/atypical protein kinase C (aPKC) signaling. Proc Natl Acad Sci U S A. 2011;108:E952-61 pubmed publisher
    ..These results demonstrate that Sirt2 controls an essential polarity pathway in SCs during myelin assembly and provide insights into the association between intracellular metabolism and SC plasticity. ..
  7. Pereira J, Lebrun Julien F, Suter U. Molecular mechanisms regulating myelination in the peripheral nervous system. Trends Neurosci. 2012;35:123-34 pubmed publisher
  8. Wergeland S, Torkildsen Ø, Myhr K, Aksnes L, Mørk S, Bø L. Dietary vitamin D3 supplements reduce demyelination in the cuprizone model. PLoS ONE. 2011;6:e26262 pubmed publisher
    ..In conclusion, high dietary doses of vitamin D3 reduce the extent of demyelination, and attenuate microglia activation and macrophage infiltration in a toxic model of demyelination, independent of lymphocyte infiltration. ..
  9. Winters J, Ferguson C, Lenk G, Giger Mateeva V, Shrager P, Meisler M, et al. Congenital CNS hypomyelination in the Fig4 null mouse is rescued by neuronal expression of the PI(3,5)P(2) phosphatase Fig4. J Neurosci. 2011;31:17736-51 pubmed publisher
  10. Arevalo Martin A, Molina Holgado E, Guaza C. A CB?/CB? receptor agonist, WIN 55,212-2, exerts its therapeutic effect in a viral autoimmune model of multiple sclerosis by restoring self-tolerance to myelin. Neuropharmacology. 2012;63:385-93 pubmed publisher
    ..These findings demonstrate for the first time that the suppression of autoimmune responses to myelin antigens underlies the therapeutic effect of CB?/CB? cannabinoid agonists in the treatment of multiple sclerosis. ..
  11. Carbajal K, Miranda J, Tsukamoto M, Lane T. CXCR4 signaling regulates remyelination by endogenous oligodendrocyte progenitor cells in a viral model of demyelination. Glia. 2011;59:1813-21 pubmed publisher
    ..These findings highlight the possibility to manipulate OPCs in order to increase the pool of remyelination-competent cells that can participate in recovery. ..
  12. Rotshenker S. Wallerian degeneration: the innate-immune response to traumatic nerve injury. J Neuroinflammation. 2011;8:109 pubmed publisher
    ..Wallerian degeneration serves as a prelude for successful repair when these requirements are met. In contrast, functional recovery is poor when injury fails to produce the efficient innate-immune response of Wallerian degeneration...
  13. Ishii A, Furusho M, Bansal R. Sustained activation of ERK1/2 MAPK in oligodendrocytes and schwann cells enhances myelin growth and stimulates oligodendrocyte progenitor expansion. J Neurosci. 2013;33:175-86 pubmed publisher
    ..Furthermore, Schwann cells with activated ERK1/2 hypermyelinate PNS axons, suggesting that ERK1/2 signaling is a conserved mechanism that promotes both CNS and PNS developmental myelination. ..
  14. Czopka T, Lyons D. Dissecting mechanisms of myelinated axon formation using zebrafish. Methods Cell Biol. 2011;105:25-62 pubmed publisher
    The myelin sheath is an essential component of the vertebrate nervous system, and its disruption causes numerous diseases, including multiple sclerosis (MS), and neurodegeneration...
  15. Wu L, Williams A, Delaney A, Sherman D, Brophy P. Increasing internodal distance in myelinated nerves accelerates nerve conduction to a flat maximum. Curr Biol. 2012;22:1957-61 pubmed publisher
  16. Chong S, Rosenberg S, Fancy S, Zhao C, Shen Y, Hahn A, et al. Neurite outgrowth inhibitor Nogo-A establishes spatial segregation and extent of oligodendrocyte myelination. Proc Natl Acad Sci U S A. 2012;109:1299-304 pubmed publisher
    ..Maximizing the myelinogenic potential of oligodendrocytes may offer an effective strategy for repair in future therapies for demyelination. ..
  17. Peters A, Kemper T. A review of the structural alterations in the cerebral hemispheres of the aging rhesus monkey. Neurobiol Aging. 2012;33:2357-72 pubmed publisher
  18. Lee Y, Morrison B, Li Y, Lengacher S, Farah M, Hoffman P, et al. Oligodendroglia metabolically support axons and contribute to neurodegeneration. Nature. 2012;487:443-8 pubmed publisher
    ..The role of oligodendroglia in axon function and neuron survival has been elusive; this study defines a new fundamental mechanism by which oligodendroglia support neurons and axons...
  19. Wake H, Lee P, Fields R. Control of local protein synthesis and initial events in myelination by action potentials. Science. 2011;333:1647-51 pubmed publisher between oligodendrocytes and axons, and increasing local synthesis of the major protein in the myelin sheath, myelin basic protein, through Fyn kinase-dependent signaling...
  20. Young K, Psachoulia K, Tripathi R, Dunn S, Cossell L, Attwell D, et al. Oligodendrocyte dynamics in the healthy adult CNS: evidence for myelin remodeling. Neuron. 2013;77:873-85 pubmed publisher
    ..The latter would predict that average internode length should decrease with age. Consistent with that, we found that adult-born OLs elaborated much shorter but many more internodes than OLs generated during early postnatal life. ..
  21. Powers B, Lasiene J, Plemel J, Shupe L, Perlmutter S, Tetzlaff W, et al. Axonal thinning and extensive remyelination without chronic demyelination in spinal injured rats. J Neurosci. 2012;32:5120-5 pubmed publisher
    ..In conclusion, we do not find a large chronically demyelinated population to target with remyelination therapies. Interventions may be better focused on correcting structural or molecular abnormalities of regenerated myelin...
  22. Li C, Xiao L, Liu X, Yang W, Shen W, Hu C, et al. A functional role of NMDA receptor in regulating the differentiation of oligodendrocyte precursor cells and remyelination. Glia. 2013;61:732-49 pubmed publisher
    ..Together, these results indicate that NMDAR plays a critical role in the regulation of OPCs differentiation in vitro and remyelination in cuprizone model which may provide potential target for the treatment of demyelination disease. ..
  23. Piao J, Wang Y, Duncan I. CD44 is required for the migration of transplanted oligodendrocyte progenitor cells to focal inflammatory demyelinating lesions in the spinal cord. Glia. 2013;61:361-7 pubmed publisher
    ..These findings suggest that CD44 is a key molecule in the migration of OPCs toward the focal inflammatory demyelinated lesion induced by zymosan, and may be an important in OPC repair in MS. ..
  24. Makinodan M, Rosen K, Ito S, Corfas G. A critical period for social experience-dependent oligodendrocyte maturation and myelination. Science. 2012;337:1357-60 pubmed publisher
  25. Senoo H, Wang H, Araki T, Williams J, Fukuzawa M. An orthologue of the Myelin-gene Regulatory Transcription Factor regulates Dictyostelium prestalk differentiation. Int J Dev Biol. 2012;56:325-32 pubmed publisher
    ..These results provide a first insight into the intracellular signaling pathway that directs pstA differentiation and identify a non-metazoan orthologue of a family of molecularly uncharacterised transcription factors...
  26. Colognato H, Tzvetanova I. Glia unglued: how signals from the extracellular matrix regulate the development of myelinating glia. Dev Neurobiol. 2011;71:924-55 pubmed publisher
    ..the myelinating glia of the PNS and CNS, respectively, as well as in the construction and maintenance of the myelin sheath itself...
  27. van der Star B, Vogel D, Kipp M, Puentes F, Baker D, Amor S. In vitro and in vivo models of multiple sclerosis. CNS Neurol Disord Drug Targets. 2012;11:570-88 pubmed
    ..Finally, we provide guidance for using and reporting animal studies with the aim of improving translational studies to the clinic. ..
  28. Kitzler H, Su J, Zeineh M, Harper Little C, Leung A, Kremenchutzky M, et al. Deficient MWF mapping in multiple sclerosis using 3D whole-brain multi-component relaxation MRI. Neuroimage. 2012;59:2670-7 pubmed publisher
    ..Further investigation will determine if this measure can serve as a risk factor for the conversion into definite MS and for the secondary transition into irreversible disease progression. ..
  29. Salzer J. Axonal regulation of Schwann cell ensheathment and myelination. J Peripher Nerv Syst. 2012;17 Suppl 3:14-9 pubmed publisher
    ..Elucidation of these signals, and the intracellular pathways they regulate, may lead to new, rational therapies for the treatment of inherited and acquired neuropathies. ..
  30. Koenning M, Jackson S, Hay C, Faux C, Kilpatrick T, Willingham M, et al. Myelin gene regulatory factor is required for maintenance of myelin and mature oligodendrocyte identity in the adult CNS. J Neurosci. 2012;32:12528-42 pubmed publisher
    ..These results demonstrate that ongoing expression of MRF within the adult CNS is critical to maintain mature oligodendrocyte identity and the integrity of CNS myelin. ..
  31. Fünfschilling U, Supplie L, Mahad D, Boretius S, Saab A, Edgar J, et al. Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity. Nature. 2012;485:517-21 pubmed publisher
    ..Because myelinated axons can use lactate when energy-deprived, our findings suggest a model in which axon-glia metabolic coupling serves a physiological function. ..
  32. Sherman D, Krols M, Wu L, Grove M, Nave K, Gangloff Y, et al. Arrest of myelination and reduced axon growth when Schwann cells lack mTOR. J Neurosci. 2012;32:1817-25 pubmed publisher
    ..The myelin sheath in the mutant was much thinner than normal; nevertheless, sheath thickness relative to axon diameter (g-ratio) ..
  33. Shi R, Rickett T, Sun W. Acrolein-mediated injury in nervous system trauma and diseases. Mol Nutr Food Res. 2011;55:1320-31 pubmed publisher
    ..Hydralazine in particular can reduce acrolein concentrations and inhibit acrolein-mediated pathologies in vivo. Acrolein scavenging appears to be a novel effective treatment, which is primed for rapid translation to the clinic...
  34. Leibinger M, Andreadaki A, Fischer D. Role of mTOR in neuroprotection and axon regeneration after inflammatory stimulation. Neurobiol Dis. 2012;46:314-24 pubmed publisher
  35. Barnett S, Linington C. Myelination: do astrocytes play a role?. Neuroscientist. 2013;19:442-50 pubmed publisher
    ..This review will focus on how this new understanding may be exploited to develop new strategies to enhance remyelination in multiple sclerosis and other diseases. ..
  36. Goldman S, Nedergaard M, Windrem M. Glial progenitor cell-based treatment and modeling of neurological disease. Science. 2012;338:491-5 pubmed publisher
  37. Stassart R, Fledrich R, Velanac V, Brinkmann B, Schwab M, Meijer D, et al. A role for Schwann cell-derived neuregulin-1 in remyelination. Nat Neurosci. 2013;16:48-54 pubmed publisher
    ..We suggest a model in which loss of axonal contact triggers denervated Schwann cells to transiently express NRG1 as an autocrine/paracrine signal that promotes Schwann cell differentiation and remyelination. ..
  38. Furusho M, Dupree J, Nave K, Bansal R. Fibroblast growth factor receptor signaling in oligodendrocytes regulates myelin sheath thickness. J Neurosci. 2012;32:6631-41 pubmed publisher
    ..Throughout adulthood, the myelin sheath remained disproportionately thin relative to the axon caliber...
  39. Chen Y, Yi Q, Liu G, Shen X, Xuan L, Tian Y. Cerebral white matter injury and damage to myelin sheath following whole-brain ischemia. Brain Res. 2013;1495:11-7 pubmed publisher
    b>Myelin sheath, either in white matter or in other regions of brain, is vulnerable to ischemia. The specific events involved in the progression of ischemia in white matter have not yet been elucidated...
  40. Silvestroff L, Bartucci S, Pasquini J, Franco P. Cuprizone-induced demyelination in the rat cerebral cortex and thyroid hormone effects on cortical remyelination. Exp Neurol. 2012;235:357-67 pubmed publisher
    ..Our results suggest that manipulation of TH levels could be considered as a strategy to promote remyelination process in the cortex and to prevent neuronal irreversible damage in patients suffering from MS. ..
  41. Ruckh J, Zhao J, Shadrach J, van Wijngaarden P, Rao T, Wagers A, et al. Rejuvenation of regeneration in the aging central nervous system. Cell Stem Cell. 2012;10:96-103 pubmed publisher
    ..These data suggest that enhanced remyelinating activity requires both youthful monocytes and other factors, and that remyelination-enhancing therapies targeting endogenous cells can be effective throughout life. ..
  42. Lee S, Leach M, Redmond S, Chong S, Mellon S, Tuck S, et al. A culture system to study oligodendrocyte myelination processes using engineered nanofibers. Nat Methods. 2012;9:917-22 pubmed publisher
    ..The use of nanofiber scaffolds will enable screening for potential therapeutic agents that promote oligodendrocyte differentiation and myelination and will also provide valuable insight into the processes involved in remyelination. ..
  43. Deoni S, Dean D, O Muircheartaigh J, Dirks H, Jerskey B. Investigating white matter development in infancy and early childhood using myelin water faction and relaxation time mapping. Neuroimage. 2012;63:1038-53 pubmed publisher
    ..Comparison of T(1), T(2) and MWF measurements demonstrates dissimilar sensitivity to tissue changes associated with neurodevelopment, with each providing differential but complementary information. ..
  44. Jarjour A, Zhang H, Bauer N, Ffrench Constant C, Williams A. In vitro modeling of central nervous system myelination and remyelination. Glia. 2012;60:1-12 pubmed publisher
    ..We discuss the difficulty and importance of quantification of myelination and in particular remyelination. Finally, we provide our predictions of how these techniques will and should develop in the future. ..
  45. Zhu H, Zhao L, Wang E, Dimova N, Liu G, Feng Y, et al. The QKI-PLP pathway controls SIRT2 abundance in CNS myelin. Glia. 2012;60:69-82 pubmed publisher
    ..Collectively, our results indicate that the abundance of SIRT2 in myelin is dependent on PLP, but not DM20. ..
  46. Buser J, Maire J, Riddle A, Gong X, Nguyen T, Nelson K, et al. Arrested preoligodendrocyte maturation contributes to myelination failure in premature infants. Ann Neurol. 2012;71:93-109 pubmed publisher
    ..PreOL maturation arrest converts chronic WMI to a more immature state related to the burden of astrogliosis. ..
  47. Hung H, Kohnken R, Svaren J. The nucleosome remodeling and deacetylase chromatin remodeling (NuRD) complex is required for peripheral nerve myelination. J Neurosci. 2012;32:1517-27 pubmed publisher
  48. Patel J, Williams J, Muccigrosso M, Liu L, Sun T, Rubin J, et al. Astrocyte TNFR2 is required for CXCL12-mediated regulation of oligodendrocyte progenitor proliferation and differentiation within the adult CNS. Acta Neuropathol. 2012;124:847-60 pubmed publisher
    ..In addition, gene delivery of critical pro-myelinating proteins might be a feasible approach for the treatment of remyelination failure in MS. ..
  49. Glasser M, Van Essen D. Mapping human cortical areas in vivo based on myelin content as revealed by T1- and T2-weighted MRI. J Neurosci. 2011;31:11597-616 pubmed publisher
  50. Marom L, Ulitsky I, Cabilly Y, Shamir R, Elroy Stein O. A point mutation in translation initiation factor eIF2B leads to function--and time-specific changes in brain gene expression. PLoS ONE. 2011;6:e26992 pubmed publisher
    ..The differentially expressed genes seem to reflect delayed waves of gene expression as well as an adaptation process to cope with hypersensitivity to cellular stress. ..
  51. Ben Arous J, Binding J, Léger J, Casado M, Topilko P, Gigan S, et al. Single myelin fiber imaging in living rodents without labeling by deep optical coherence microscopy. J Biomed Opt. 2011;16:116012 pubmed publisher
    b>Myelin sheath disruption is responsible for multiple neuropathies in the central and peripheral nervous system. Myelin imaging has thus become an important diagnosis tool...
  52. Jepson S, Vought B, Gross C, Gan L, Austen D, Frantz J, et al. LINGO-1, a transmembrane signaling protein, inhibits oligodendrocyte differentiation and myelination through intercellular self-interactions. J Biol Chem. 2012;287:22184-95 pubmed publisher
    ..Disruption of this protein-protein interaction could lead to a decrease of LINGO-1 inhibition and an increase in myelination. ..
  53. Duffy P, Wang X, Siegel C, Seigel C, Tu N, Henkemeyer M, et al. Myelin-derived ephrinB3 restricts axonal regeneration and recovery after adult CNS injury. Proc Natl Acad Sci U S A. 2012;109:5063-8 pubmed publisher
    ..Thus, ephrinB3 contributes to myelin-derived axonal growth inhibition and limits recovery from adult CNS trauma. ..