Multiple sclerosis (MS) is characterized by multiple neurological deficits reflecting lesions in multiple parts of the CNS. It has a relapsing–remitting course in some patients, and a progressive course in others.
Remissions in MS occur in the context of demyelination of CNS axons, which causes conduction failure, followed by restoration of conduction due to the expression of voltage-gated sodium channels (probably Nav1.2 channels) along denuded axon regions that previously lacked Na+ channels.
Disease progression (acquisition of persistent, non-remitting neurological deficits) in MS is due, in large part, to degeneration of axons in the CNS.
Sustained Na+ influx through Na+ channels (probably Nav1.6 channels) seems to drive reverse Na+/Ca2+ exchange, which imports injurious levels of Ca2+ into axons in MS, contributing to axonal degeneration.
Aberrant expression of sensory neuron specific Nav1.8 channels in cerebellar Purkinje neurons in MS appears to perturb their firing patterns. This might contribute to loss of coordination in MS.
Sodium channels also seem to have a role in the activation of, and phagocytosis by, macrophages and microglia in MS.
The identification of distinct pathophysiological roles of different Na+ channel isoforms suggests that it might be possible to develop therapies that target these channel isoforms so as to prevent axonal degeneration, reduce inflammation and/or ameliorate neuronal mistuning in MS.
Multiple sclerosis (MS) is the most common cause of neurological disability in young adults. Recent studies have implicated specific sodium channel isoforms as having an important role in several aspects of the pathophysiology of MS, including the restoration of impulse conduction after demyelination, axonal degeneration and the mistuning of Purkinje neurons that leads to cerebellar dysfunction. By manipulating the activity of these channels or their expression, it might be possible to develop new therapeutic approaches that will prevent or limit disability in MS.
Your institute does not have access to this article
Open Access articles citing this article.
Molecular Brain Open Access 20 July 2022
Cell Regeneration Open Access 02 June 2021
Enhanced axonal response of mitochondria to demyelination offers neuroprotection: implications for multiple sclerosis
Acta Neuropathologica Open Access 22 June 2020
Subscribe to Journal
Get full journal access for 1 year
only $4.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Ritchie, J. M. & Rogart, R. B. The density of sodium channels in mammalian myelinated nerve fibers and the nature of the axonal membrane under the myelin sheath. Proc. Natl Acad. Sci. USA 74, 211–215 (1997).
Waxman, S. G. Conduction in myelinated, unmyelinated, and demyelinated fibers. Arch. Neurol. 34, 585–590 (1977). Together with reference 1, this paper showed the focal distribution of Na+ channels, which are aggregated in the nodal axon membrane of myelinated axons.
Ulrich, J. & Groebke-Lorenz, W. The optic nerve in MS: a morphological study with retrospective clinicopathological correlation. Neurol. Ophthalmol. 3, 149–159 (1983).
Bostock, H. & Sears, T. A. The internodal axon membrane: electrical excitability and continuous conduction in segmental demyelination. J. Physiol. 280, 273–301 (1978).
Foster, R. E., Whalen, C. C. & Waxman, S. G. Reorganization of the axonal membrane of demyelinated nerve fibers: morphological evidence. Science 210, 661–663 (1980). Together with reference 4, this paper showed reorganization of the demyelinated axon membrane, which acquires Na+ channels in densities sufficient to support conduction.
Novakovic, S. D., Levinson, S. R., Schachner, M. & Shrager, P. Disruption and reorganization of sodium channels in experimental allergic neuritis. Muscle Nerve 21, 1019–1032 (1998).
England, J. D., Gamboni, F. & Levinson, S. R. Increased numbers of sodium channels form along demyelinated axons. Brain Res. 548, 334–337 (1991).
Moll, C., Mouvre, C., Lazdunski, M. & Ulrich, J. Increase of sodium channels in demyelinated lesions of multiple sclerosis. Brain Res. 556, 311–316 (1991).
Trapp, B. D. et al. Axonal transection in the lesions of multiple sclerosis. New Engl. J. Med. 338, 278–285 (1998). Discusses the time course and the frequency of axonal degeneration in MS.
Kuhlmann, T., Lingfeld, G., Bitsch, A., Schuchardt, J. & Bruck, W. Acute axonal damage in multiple sclerosis is most extensive in early disease stages and decreases over time. Brain 125, 2202–2212 (2002).
Davie, C. et al. Functional deficit in multiple sclerosis and autosomal dominant cerebellar ataxia is associated with axon loss. Brain 118, 1583–1592 (1995).
Wujek, J. R. et al. Axon loss in the spinal cord determines permanent neurological disability in an animal model of multiple sclerosis. J. Neuropathol. Exp. Neurol. 61, 23–32 (2002).
Stys, P. K., Waxman, S. G. & Ransom, B. R. Ionic mechanisms of anoxic injury in mammalian CNS white matter: role of Na+ channels and Na+–Ca2+ exchanger. J. Neurosci. 12, 430–439 (1992). Demonstration that a persistent Na+ influx drives reverse Na+–Ca2+ exchange which injures axons.
Stys, P. K., Sontheimer, H., Ransom, B. R. & Waxman, S. G. Noninactivating, tetrodotoxin-sensitive Na+ conductance in rat optic nerve axons. Proc. Natl Acad. Sci. USA 90, 6976–6980 (1993).
LoPachin, R. M. Jr & Stys, P. K. Elemental composition and water content of rat optic nerve myelinated axons and glial cells: effects of in vitro anoxia and reoxygenation J. Neurosci. 15, 6735–6746 (1995).
Stys, P. K., Ransom, B. R. & Waxman, S. G. Tertiary and quaternary local anesthetics protect CNS white matter from anoxic injury at concentrations that do not block excitability. J. Neurophysiol. 67, 236–240 (1992).
Fern, R., Ransom, B. R., Stys, P. K. & Waxman, S. G. Pharmacological protection of CNS white matter during anoxia: actions of phenytoin, carbamazepine and diazepam. J. Pharmacol. Exper. Ther. 266, 1549–1555 (1993).
Lo, A. C., Black, J. A. & Waxman, S. G. Phenytoin protects spinal cord axons and preserves axonal conduction and neurological function in a model of neuroinflammation in vivo. J. Neurophysiol. 90, 3566–3572 (2003).
Bechtold, D. A., Kapoor, R. & Smith, K. J. Axonal protection using flecainide in experimental autoimmune encephalomyelitis. Ann. Neurol. 55, 607–616 (2004). Along with reference 18, this paper demonstrates protection of axons in EAE with Na+ channel blockers.
Smith, K. J. & Lassmann, H. The role of NO in multiple sclerosis. Lancet Neurol. 1, 232–241 (2002).
Brown, G. C. & Bal-Price, A. Inflammatory neurodegeneration mediated by nitric oxide, glutamate, and mitochondria. Mol. Neurobiol. 27, 325–355 (1989).
Kapoor, R., Davies, M., Blaker, P. A., Hall, S. M. & Smith, K. J. Blockers of sodium and calcium entry protect axons from nitric oxide-mediated degeneration. Ann. Neurol. 53, 174–180 (2003). Shows that Na+ channel blockers protect axons from NO-induced injury.
Garthwaite, G., Goodwin, D. A., Batchelor, A. M., Leeming, K. & Garthwaite, J. Nitric oxide toxicity in CNS white matter: an in vitro study using rat optic nerve. Neuroscience 109, 145–155 (2002).
Dutta R. et al. Mitochondrial dysfunction as a cause of axonal degeneration in multiple sclerosis patients. Ann. Neurol. 59, 478–489 (2006).
Catterall W. A., Goldin A. L & Waxman, S. G. International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels. Pharmacol. Rev. 57, 397–409 (2005).
Waxman, S. G., Black, J. A., Kocsis, J. D. & Ritchie, J. M. Low density of sodium channels supports action potential conduction in axons of neonatal rat optic nerve. Proc. Natl Acad. Sci. USA 86, 1406–1410 (1989).
Boiko, T. et al. Compact myelin dictates the differential targeting of two sodium channel isoforms in the same axon. Neuron 30, 91–104 (2001).
Kaplan, M. R. et al. Differential control of clustering of the sodium channels Nav1.2 and Nav1.6 at developing CNS nodes of Ranvier. Neuron 30, 105–119 (2001).
Foster, R. E., Connors, B. R. & Waxman, S. G. Rat optic nerve: electrophysiological, pharmacological and anatomical studies during development. Dev. Brain Res. 3, 361–376 (1982).
Rasband, M. N. et al. Dependence of nodal sodium channel clustering on paranodal axo-glial contact in the developing CNS. J. Neurosci. 19, 7516–7528 (1999).
Westenbroek, R. E., Merrick, D. K. & Catteral, W. A. Differential subcellular localization of the RI and RII Na+ channel subtypes in central neurons. Neuron 3, 695–704 (1989).
Boiko, T. et al. Functional specialization of the axon initial segment by isoform-specific sodium channel targeting. J. Neurosci. 23, 2306–2313 (2003).
Caldwell, J. H., Schaller, K. L., Lasher, R. S., Peles, E. & Levinson, S. D. Sodium channel Nav1.6 is localized at nodes of Ranvier, dendrites, and synapses. Proc. Natl Acad. Sci. USA 97, 5616–5620 (2000). Demonstration that Nav1.6 is the predominant Na+ channel at the nodes of Ranvier.
Craner, M. J., Lo, A. C., Black, J. A. & Waxman, S. G. Abnormal sodium channel distribution in optic nerve axons in a model of inflammatory demyelination. Brain 126, 1552–1562 (2003).
Craner, M. J., Hains, B. C., Lo, A. C., Black, J. A. & Waxman S. G. Colocalization of sodium channel Nav1.6 and the sodium-calcium exchanger at sites of axonal injury in the spinal cord in EAE. Brain 127, 294–303 (2004). Together with reference 34, this paper identifies the Na+ channel isoforms along demyelinated CNS axons in EAE, and shows the association of Nav1.6 with axonal injury.
Black, J. A. et al. Upregulation of a silent sodium channel after peripheral, but not central, nerve injury in DRG neurons. J. Neurophysiol. 82, 2776–2785 (1999).
Rush, A. M., Dib-Hajj, S. D. & Waxman, S. G. Electrophysiological properties of two axonal sodium channels, Nav1.2 and Nav1.6, expressed in spinal sensory neurons. J. Physiol. 564, 803–816 (2005).
Lassmann, H. in Multiple Sclerosis as a Neuronal Disease (ed. Waxman, S. G.) 153–165 (Elsevier Science, Amsterdam, 2005).
Craner, M. J. et al. Molecular changes in neurons in MS: altered axonal expression of Nav1.2 and Nav1.6 sodium channels and Na+/Ca2+ exchanger. Proc. Natl Acad. Sci. USA 101, 8168–8173 (2004). Identifies the Na+ channel isoforms along demyelinated axons in MS.
Bhat, M. A. et al. Axon–glia interactions and the domain organization of myelinated axons requires neurexin IV/Caspr/ Paranodin. Neuron 30, 369–383 (2001).
Gong, B., Rhodes, J., Bekele-Arcuri, Z. & Trimmer, J. S. Type I and type II Na+ channel α-subunit polypeptides exhibit distinct spatial and temporal patterning, and association with auxiliary subunits in rat brain. J. Comp. Neurol. 412, 342–352 (1999).
Whitaker, W. R. et al. Distribution of voltage-gated sodium channel α-subunit and β-subunit mRNAs in human hippocampal formation, cortex, and cerebellum. J. Comp. Neurol. 422, 123–139 (2000).
Iwata, A. et al. Traumatic axonal injury induces proteolytic cleavage of the voltage-gated sodium channels modulated by tetrodotoxin and protease inhibitors. J. Neurosci. 24, 4605–4613 (2004).
Herzog, R. I., Liu, C., Waxman, S. G. & Cummins, T. R. Calmodulin binds to the C terminus of sodium channels Nav1.4 and Nav1.6 and differentially modulates their functional properties. J. Neurosci. 23, 8261–8270 (2003).
Waxman, S. G., Davis, P. K., Black, J. A. & Ransom, B. R. Anoxic injury of mammalian central white matter: decreased susceptibility in myelin-deficient optic nerve. Ann. Neurol. 28, 335–340 (1990).
Imaizumi, T., Kocsis, J. D. & Waxman, S. G. Resistance to anoxic injury in rat spinal cord following demyelination. Brain Res. 779, 292–296 (1998).
DeLuca, G. C., Williams, K., Evangelou, N., Ebers, G. C. & Esiri, M. M. The contribution of demyelination to axonal loss in multiple sclerosis. Brain 129, 1507–1516 (2006).
Steffensen, I., Waxman, S. G., Mills, L. & Stys, P. K. Immunolocalization of the Na+– Ca2+ exchanger in mammalian myelinated axons. Brain Res. 776, 1–9 (1997).
Matthews, W. B., Compston, A., Allen, I. V. & Martyn, C. N. McAlpine's Multiple Sclerosis (Churchill Livingstone, New York, 1991).
Andermann, F., Cosgrove, J. B. R., Lloyd-Smith, D. & Walters, A. M. Paroxysmal dysarthria and ataxia in multiple sclerosis; a report of 2 unusual cases. Neurology 9, 211–215 (1959).
Espir, M. L., Watkins, S. M. & Smith, H. V. Paroxysmal dysarthria and other transient neurological disturbances in disseminated sclerosis. J. Neurol. Neurosurg. Psychiat. 29, 323–330 (1966).
Waxman, S. G. Cerebellar dysfunction in multiple sclerosis: evidence for an acquired channelopathy. Prog. Brain Res. 148, 353–365 (2005).
Black, J. A. et al. Abnormal expression of SNS/PN3 sodium channel in cerebellar Purkinje cells following loss of myelin in the Taiep rat. NeuroReport 10, 913–918 (1999).
Black, J. A. et al. Sensory neuron specific sodium channel SNS is abnormally expressed in the brains of mice with experimental allergic encephalomyelitis and humans with multiple sclerosis. Proc. Natl Acad. Sci. 97, 11598–11602 (2000). Demonstration of aberrant expression of the SNS Na+ channel Nav1.8 in Purkinje cells in EAE and MS.
Okuse, K. et al. AnnexinII light chain regulates sensory neuron-specific sodium channel expression. Nature 47, 653–656 (2002).
Craner, M. J. et al. Annexin II/p11 is up-regulated in Purkinje cells in EAE and MS. NeuroReport 14, 555–558 (2003).
Akopian, A. N., Sivilotti, L. & Wood, J. N. A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons. Nature 379, 257–262 (1996).
Sangameswaren, L. et al. Structure and function of a novel voltage-gated tetrodotoxin-resistant sodium channel specific to sensory neurons. J. Biol. Chem. 271, 5953–5956 (1996).
Elliott, A. A. & Elliott, J. R. Characterization of TTX-sensitive and TTX-resistant sodium currents in small cells from adult rat dorsal root ganglia. J. Physiol. (Lond.) 463, 93–56 (1993).
Dib-Hajj, S. D., Ishikawa, I., Cummins, T. R. & Waxman, S. G. Insertion of an SNS-specific tetrapeptide in the S3–S4 linker of D4 accelerates recovery from inactivation of skeletal muscle voltage-gated Na channel μ1 in HEK293 cells. FEBS Letts. 416, 11–14 (1997).
Renganathan, M., Cummins, T. R. & Waxman, S. G. The contribution of Nav1.8 sodium channels to action potential electrogenesis in DRG neurons. J. Neurophysiol. 86, 629–640 (2001).
Blair, N. T. & Bean, B. P. Roles of tetrodotoxin (TTX)-Sensitive Na+ current TTX-resistent Na+ current and Ca2+ current in the action potentials of nociceptive sensory neurons. J. Neurosci. 22, 10277–10290 (2002).
Llinas, R. & Sugimori, M. Electrophysiological properties of in vitro Purkinje cell somata in mammalian cerebellar slices J. Physiol. 305, 171–195 (1980).
Stuart, G. & Hausser, M. Initiation and spread of sodium action potentials in cerebellar purkinje cells. Neuron 13, 703–712 (1994).
Raman, I. M., Sprunger, L. K., Meisler, M. H. & Bean, B. P. Altered subthreshold sodium currents and disrupted firing patterns in Purkinje neurons of Scn81 mutant mice. Neuron 19, 881–891 (1997).
Kohrman, D. C., Smith, M. R., Goldin, A. L., Harris, J. & Meisler, M. H. A missense mutation in the sodium channel Scn8a is responsible for cerebellar ataxia in the mouse mutant jolting. J. Neurosci. 16, 5993–5999 (1996).
Renganathan, M., Gelderblom, M., Black, J. A. & Waxman, S. G. Expression of Nav1.8 sodium channels perturbs the firing patterns of cerebellar Purkinje cells. Brain Res. 959, 235–243 (2003).
Saab, C. V., Craner, M. J., Kataoka, Y. & Waxman, S. G. Abnormal Purkinje cell activity in vivo in experimental allergic encephalomyelitis, in preparation. Exp. Brain Res. 158, 1–8 (2004).
Black, J. A., Langworthy, K., Hinson, A. W., Dib-Haii, S. & Waxman, S. G. NGF has opposing effects on Na+ channel III and SNS gene expression in spinal sensory neurons. Neuroreport 8, 2331–2335 (1997).
Dib-Hajj, S. D. et al. Rescue of α-SNS sodium channel expression in small dorsal root ganglion neurons after axotomy by nerve growth factor in vivo. Neurophysiology 79, 2668–2676 (1998).
Laudiero, L. B. et al. Multiple sclerosis patients express increased levels of β-nerve growth factor in cerebrospinal fluid. Neurosci. Lett. 147, 9–12 (1992).
DeSimone, R., Micera, A., Tirassa, P. & Aloe, L. mRNA for NGF and p75 in the central nervous system of rats affected by experimental allergic encephalomyelitis. Neuropathol. Appl. Neurobiol. 22, 54–59 (1996).
Damarjian, T. G., Craner, M. J., Black, J. A. & Waxman, S. G. Upregulation and colocalization of p75 and Nav1.8 in Purkinje neurons in experimental autoimmune encephalomyelitis. Neurosci. Lett. 369, 186–190 (2004).
Muragaki, Y. et al. Expression of trk receptors in the developing and adult human central and peripheral nervous system J. Comp. Neurol. 356, 387–397 (1995).
Yan, Q. & Johnson, E. M. Jr. An immunohistochemical study of the nerve growth factor receptor in developing rats. J. Neurosci. 8, 3481–3498 (1988).
Soilu-Hanninen, M. et al. Treatment of experimental autoimmune encephalomyelitis with antisense oligonucleotides against the low affinity neurotrophin receptor. J. Neurosci. Res. 59, 712–721 (2001).
Craner, M. J. et al. Sodium channels contribute to microglia/macrophage activation and function in EAE and MS. Glia, 49, 220–229 (2005). Demonstration of upregulated expression of Nav1.6 channels in microglia and macrophages in EAE and MS, and of their role in microglial/macrophage activation and phagocytosis.
Ferguson, B., Matyszak, M. K., Esiri, M. M. & Perry, V. H. Axonal damage in acute multiple sclerosis lesions. Brain 120, 393–399 (1997).
Kornek, B. et al. Multiple sclerosis and chronic autoimmuno encephalomyelitis: a comparative quantitative study of axonal injury in active, inactive and remyelinated lesions. Am. J. Pathol. 157, 267–276 (2000).
Cash, E. & Rott, O. Microglial cells qualify as the stimulators of unprimed CD4+ and CD8+T lymphocytes in the cenetral nervous system. Clin. Exp. Immunol. 98, 313–318 (1994).
Renno, T., Krakowski, M., Piccirillo, C., Lin, J. Y. & Owens, T. TNF-α expression by resident microglia and infiltrating leukocytes in the central nervous system of mice with experimental allergic encephalomyelitis. Regulation by Th1 cytokines. J. Immunol. 154, 944–953 (1995).
Hooper, D. C. et al. Prevention of experimental allergic encephalomyelitis by targeting nitric oxide and peroxynitrite: implications for the treatment of multiple sclerosis. Proc. Natl Acad. Sci. USA 94, 2528–2533 (1997).
DeGroot, C. J. et al. Immunocytochemical characterization of the expression of inducible and constitutive isoforms of netric oxide synthase in demyelinating multiple sclerosis lesions. Neuropathol. Exp. Neurol. 56, 10–20 (1997).
Matsumoto Y., Ohmori, Y. & Fujiwara, K. Immune regulation by brain cells in the central nervous system: microglia but not astrocytes present myelin basic protein to encephalitogenic T cells under in vivo-mimicking conditions. Immunology 76, 209–216 (1992).
Li, H., Cuzner, M. L. & Newcombe, J. Microglia-derived macrophages in early multiple sclerosis plaques. Neuropathol. Appl. Neurobiol. 22, 207–215 (1996).
Korotzer, A. R. & Cotman, C. W. Voltage-gated currents expressed by rat microglia in culture. Glia 6, 81–88 (1992).
Nörenberg W., Illes, P. & Gebicke-Haeter, P. J. Sodium channels in isolated human brain macrophages (microglia). Glia 10, 165–172 (1994).
Black, J. A., Liu, S., Hains, B. C., Saab, C. Y. & Waxman, S. G. Long-term protection of central axons with phenytoin in monophasic and chronic-relapsing EAE. Brain 24 Aug 2006 (doi: 10.1093/brain/aw1216).
Lai, Z. F., Chen, Y. Z. & Nishimura, Y. An amiloride-sensitive and voltage-dependent Na+ channel in an HLA-DR-restricted human T cell clone. J. Immunol. 165, 83–90 (2000).
Khan, N. A. & Poisson, J. P. 5-HT3 receptor-channels coupled with Na+ influx in human T cells: role in T cell activation. J. Neuroimmunol. 99, 53–60 (1999).
Waxman, S. G., Demyelination in spinal cord injury and multiple sclerosis: what can we do to enhance functional recovery? J. Neurotrauma 9, S105–S117 (1992).
Popovich, P. G. & Jones, T. B. Manipulating neuroinflammatory reactions in the injured spinal cord: back to basics. Trends Pharmacol. Sci. 24, 13–17 (2003).
Research in the author's laboratory has been supported, in part, by grants from the National Multiple Sclerosis Society and the Medical Research Service and Rehabilitation Research Service, the Department of Veteran Affairs, and by gifts from Destination Cure and the Nancy Davis Foundation. The Neuroscience and Regeneration Research Center is a Collaboration of the Paralyzed Veterans of America and the United Spinal Association with Yale University.
The author declares no competing financial interests.
- Nodes of Ranvier
Small gaps in the myelin sheath along myelinated fibres. Nodes of Ranvier extend ∼1 μm along the fibre, and are separated by segments of myelin that extend for tens or, more commonly, hundreds of micrometres.
- Internodal domains
Regions of the axon between the nodes of Ranvier.
- Saltatory conduction
A process of rapid impulse conduction that is conferred on axons by myelin sheaths, in which the action potential leaps discontinously and rapidly from one node of Ranvier to the next.
- Impedance mismatch
A phenomenon in which, owing to non-uniform properties, there is a sudden drop in electrical resistance or rise in capacitance along a cable or nerve fibre. Impedance mismatch occurs at the border between normally myelinated and demyelinated parts of axons in disorders such as multiple sclerosis, and contributes to conduction failure.
- Capacitative shield
The electrical shield provided by the myelin that surrounds the axon, which prevents loss of current through the membrane capacitance of the axon.
- Longitudinal current analysis
A method in which extracellular electrodes are used to measure electrical currents as they flow along nerve fibres and, thereby, to infer the presence of nodes or foci of node-like membrane.
- Electron microprobe
A non-invasive tool that permits the measurement of the elemental composition of tissues.
- Paranodal domain
The part of the axon, at the ends of the internodes, where the axon and the myelin form a relatively tight seal (the paranodal junction).
- Plaque load
An aggregate measure of the number and volume of lesions in a brain with multiple sclerosis.
Loss of coordination of muscle movements, produced most commonly by dysfunction of the cerebellum (cerebellar ataxia) or defective sensory input (sensory ataxia).
Disorders due to mutations of ion channels (inherited channelopathies), or due to altered channel function attributable to exposure to toxins or antibodies, or to dyregulated channel expression after tissue injury (acquired channelopathies).
The production of electrical signals — for example, action potentials — by cells such as neurons.
About this article
Cite this article
Waxman, S. Axonal conduction and injury in multiple sclerosis: the role of sodium channels. Nat Rev Neurosci 7, 932–941 (2006). https://doi.org/10.1038/nrn2023
Molecular Brain (2022)
Cell Regeneration (2021)
Chronic Demyelination and Axonal Degeneration in Multiple Sclerosis: Pathogenesis and Therapeutic Implications
Current Neurology and Neuroscience Reports (2021)
Journal of Neurology (2021)
Enhanced axonal response of mitochondria to demyelination offers neuroprotection: implications for multiple sclerosis
Acta Neuropathologica (2020)