Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Mechanisms of Disease: inherited demyelinating neuropathies—from basic to clinical research

Nature Clinical Practice Neurology volume 3, pages 453–464 (2007)Cite this article

Abstract

The hereditary motor and sensory neuropathies (also known as Charcot–Marie–Tooth disease or CMT) are characterized by a length-dependent loss of axonal integrity in the PNS, which leads to progressive muscle weakness and sensory deficits. The 'demyelinating' neuropathies (CMT disease types 1 and 4) are genetically heterogeneous, but their common feature is that the primary defect perturbs myelination. As we discuss in this Review, several new genes associated with CMT1 and CMT4 have recently been identified. The emerging view is that a range of different subcellular defects in Schwann cells can cause axonal loss, which represents the final common pathway of all CMT disease and is independent of demyelination. We propose that Schwann cells provide a first line of axonal neuroprotection. A better understanding of axon–glia interactions should open the way to therapeutic interventions for demyelinating neuropathies. Transgenic animal models have become essential for dissecting CMT disease mechanisms and exploring novel therapies.

Key Points

  • The inherited demyelinating neuropathies Charcot–Marie–Tooth (CMT) disease types 1 and 4 are genetically heterogeneous, but their common feature is that the primary defect perturbs myelination

  • All mutations that cause CMT1 have almost complete penetrance, and the mutated genes are expressed in myelinating Schwann cells

  • The products of CMT-associated genes include not only structural components of myelin, but also proteins that have signalling and regulatory functions in Schwann cells

  • Axonal loss seems to be the final common pathway of all CMT disease

  • Knowing the primary causes of demyelination and obtaining insights into the downstream mechanisms of neuropathies are the first steps towards developing rational treatment strategies for CMT disease

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The final common pathway of Charcot–Marie–Tooth disease

Similar content being viewed by others

References

  1. Shy ME et al. (2005) Principles of classifications, clinical syndromes. In Peripheral Neuropathy, edn 4 (2 vols) 1623–1658 (Eds Dyck PJ and Thomas PK) Philadelphia: Elsevier Saunders

    Google Scholar 

  2. Züchner S and Vance JM (2006) Mechanisms of disease: a molecular genetic update on hereditary axonal neuropathies. Nat Clin Pract Neurol 2: 45–53

    PubMed  Google Scholar 

  3. Killian JM et al. (1996) Longitudinal studies of the duplication form of Charcot–Marie–Tooth polyneuropathy. Muscle Nerve 19: 74–78

    CAS  PubMed  Google Scholar 

  4. Birouk N et al. (1997) Charcot–Marie–Tooth disease type 1A with 17p11.2 duplication: clinical and electrophysiological phenotype study and factors influencing disease severity in 119 cases. Brain 120: 813–823

    PubMed  Google Scholar 

  5. Krajewski K et al. (2000) Neurological dysfunction and axonal degeneration in Charcot–Marie–Tooth disease type 1A. Brain 123: 1516–1527

    PubMed  Google Scholar 

  6. Lewis RA et al. (2003) Motor unit number estimate of distal and proximal muscles in Charcot–Marie–Tooth disease. Muscle Nerve 28: 161–167

    PubMed  Google Scholar 

  7. Lawson VH et al. (2003) Assessment of axonal loss in Charcot–Marie–Tooth neuropathies. Exp Neurol 184: 753–757

    PubMed  Google Scholar 

  8. Keller MP and Chance PF (1999) Inherited neuropathies: from gene to disease. Brain Pathol 9: 327–341

    CAS  PubMed  Google Scholar 

  9. Martini R and Toyka KV (2004) Immune-mediated components of hereditary demyelinating neuropathies: lessons from animal models and patients. Lancet Neurol 3: 457–465

    PubMed  Google Scholar 

  10. Kuhlenbaumer G et al. (2002) Clinical features and molecular genetics of hereditary peripheral neuropathies. J Neurol 249: 1629–1650

    CAS  PubMed  Google Scholar 

  11. Shy ME (2004) Charcot–Marie–Tooth disease: an update. Curr Opin Neurol 17: 579–585

    CAS  PubMed  Google Scholar 

  12. Suter U and Scherer SS (2003) Disease mechanisms in inherited neuropathies. Nat Rev Neurosci 4: 714–726

    CAS  PubMed  Google Scholar 

  13. Meyer zu Horste GM and Nave KA (2006) Animal models of inherited neuropathies. Curr Opin Neurol 19: 464–473

    Google Scholar 

  14. Timmerman V et al. (2006) Molecular genetics, biology, and therapy for inherited peripheral neuropathies. Neuromolecular Med 8: 1–2

    CAS  PubMed  Google Scholar 

  15. Berger P et al. (2006) Schwann cells and the pathogenesis of inherited motor and sensory neuropathies (Charcot–Marie–Tooth disease). Glia 54: 243–257

    PubMed  Google Scholar 

  16. Szigeti K et al. (2006) Charcot–Marie–Tooth disease and related hereditary polyneuropathies: molecular diagnostics determine aspects of medical management. Genet Med 8: 86–92

    PubMed  Google Scholar 

  17. Inherited Peripheral Neuropathies Mutation Database [http://www.molgen.ua.ac.be/CMTMutations/]

  18. Skre H (1974) Genetic and clinical aspects of Charcot–Marie–Tooth's disease. Clin Genet 6: 98–118

    CAS  PubMed  Google Scholar 

  19. Boerkoel CF et al. (2002) Charcot–Marie–Tooth disease and related neuropathies: mutation distribution and genotype–phenotype correlation. Ann Neurol 51: 190–201

    CAS  PubMed  Google Scholar 

  20. Lupski JR et al. (1991) DNA duplication associated with Charcot–Marie–Tooth disease type 1A. Cell 66: 219–232

    CAS  PubMed  Google Scholar 

  21. Raeymaekers P et al. (1991) Duplication in chromosome 17p11.2 in Charcot–Marie–Tooth neuropathy type 1a (CMT 1a). The HMSN Collaborative Research Group. Neuromuscul Disord 1: 93–97

    CAS  PubMed  Google Scholar 

  22. Sereda MW et al. (2003) Therapeutic administration of progesterone antagonist in a model of Charcot–Marie–Tooth disease (CMT-1A). Nat Med 9: 1533–1537

    CAS  PubMed  Google Scholar 

  23. Passage E et al. (2004) Ascorbic acid treatment corrects the phenotype of a mouse model of Charcot–Marie–Tooth disease. Nat Med 10: 396–401

    CAS  PubMed  Google Scholar 

  24. Pareyson D et al. (2006) A multicenter, randomized, double-blind, placebo-controlled trial of long-term ascorbic acid treatment in Charcot–Marie–Tooth disease type 1A (CMT-TRIAAL): the study protocol [EudraCT no.: 2006-000032-27]. Pharmacol Res 54: 436–441

    CAS  PubMed  Google Scholar 

  25. Kaku DA et al. (1993) Nerve conduction studies in Charcot–Marie–Tooth polyneuropathy associated with a segmental duplication of chromosome 17. Neurology 43: 1806–1808

    CAS  PubMed  Google Scholar 

  26. Patel PI et al. (1992) The gene for the peripheral myelin protein PMP-22 is a candidate for Charcot–Marie–Tooth disease type 1A. Nat Genet 1: 159–165

    CAS  PubMed  Google Scholar 

  27. Timmerman V et al. (1992) The peripheral myelin protein gene PMP-22 is contained within the Charcot–Marie–Tooth disease type 1A duplication. Nat Genet 1: 171–175

    CAS  PubMed  Google Scholar 

  28. Valentijn LJ et al. (1992) The peripheral myelin gene PMP-22/GAS-3 is duplicated in Charcot–Marie–Tooth disease type 1A. Nat Genet 1: 166–170

    CAS  PubMed  Google Scholar 

  29. Pentao L et al. (1992) Charcot–Marie–Tooth type 1A duplication appears to arise from recombination at repeat sequences flanking the 1.5 Mb monomer unit. Nat Genet 2: 292–300

    CAS  PubMed  Google Scholar 

  30. Reiter LT et al. (1996) A recombination hotspot responsible for two inherited peripheral neuropathies is located near a mariner transposon-like element. Nat Genet 12: 288–297

    CAS  PubMed  Google Scholar 

  31. Chance PF et al. (1993) DNA deletion associated with hereditary neuropathy with liability to pressure palsies. Cell 72: 143–151

    CAS  PubMed  Google Scholar 

  32. Li J et al. (2004) Loss-of-function phenotype of hereditary neuropathy with liability to pressure palsies. Muscle Nerve 29: 205–210

    PubMed  Google Scholar 

  33. Suter U et al. (1992) Trembler mouse carries a point mutation in a myelin gene. Nature 356: 241–244

    CAS  PubMed  Google Scholar 

  34. Roa BB et al. (1993) Charcot–Marie–Tooth disease type 1A: association with a spontaneous point mutation in the PMP22 gene. N Engl J Med 329: 96–101

    CAS  PubMed  Google Scholar 

  35. Sereda MW et al. (1996) A transgenic rat model of Charcot–Marie–Tooth disease. Neuron 16: 1049–1060

    CAS  PubMed  Google Scholar 

  36. Huxley C et al. (1996) Construction of a mouse model of Charcot–Marie–Tooth disease type 1A by pronuclear injection of human YAC DNA. Hum Mol Genet 5: 563–569

    CAS  PubMed  Google Scholar 

  37. Adlkofer K et al. (1995) Hypermyelination and demyelinating peripheral neuropathy in Pmp22-deficient mice. Nat Genet 11: 274–280

    CAS  PubMed  Google Scholar 

  38. D'Urso D et al. (1999) Peripheral myelin protein 22 and protein zero: a novel association in peripheral nervous system myelin. J Neurosci 19: 3396–3403

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Notterpek L et al. (1999) PMP22 accumulation in aggresomes: implications for CMT1A pathology. Neurobiol Dis 6: 450–460

    CAS  PubMed  Google Scholar 

  40. Fortun J et al. (2006) Alterations in degradative pathways and protein aggregation in a neuropathy model based on PMP22 overexpression. Neurobiol Dis 22: 153–164

    CAS  PubMed  Google Scholar 

  41. Johnston JA et al. (1998) Aggresomes: a cellular response to misfolded proteins. J Cell Biol 143: 1883–1898

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Lemke G and Axel R (1985) Isolation and sequence of a cDNA encoding the major structural protein of peripheral myelin. Cell 40: 501–508

    CAS  PubMed  Google Scholar 

  43. Filbin MT et al. (1990) Role of myelin P0 protein as a homophilic adhesion molecule. Nature 344: 871–872

    CAS  PubMed  Google Scholar 

  44. Giese KP et al. (1992) Mouse P0 gene disruption leads to hypomyelination, abnormal expression of recognition molecules, and degeneration of myelin and axons. Cell 71: 565–576

    CAS  PubMed  Google Scholar 

  45. Martini R et al. (1995) Protein zero (P0)-deficient mice show myelin degeneration in peripheral nerves characteristic of inherited human neuropathies. Nat Genet 11: 281–286

    CAS  PubMed  Google Scholar 

  46. Wrabetz L et al. (2000) P(0) glycoprotein overexpression causes congenital hypomyelination of peripheral nerves. J Cell Biol 148: 1021–1034

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Yin X et al. (2000) Schwann cell myelination requires timely and precise targeting of P(0) protein. J Cell Biol 148: 1009–1020

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Wrabetz L et al. (2006) Different intracellular pathomechanisms produce diverse myelin protein zero neuropathies in transgenic mice. J Neurosci 26: 2358–2368

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Maurer M et al. (2002) Role of immune cells in animal models for inherited neuropathies: facts and visions. J Anat 200: 405–414

    PubMed  PubMed Central  Google Scholar 

  50. Ip C et al. (2006) Role of immune cells in animal models for inherited peripheral neuropathies. Neuromolecular Med 8: 175–190

    CAS  Google Scholar 

  51. Marrosu MG et al. (1998) Charcot–Marie–Tooth disease type 2 associated with mutation of the myelin protein zero gene. Neurology 50: 1397–1401

    CAS  PubMed  Google Scholar 

  52. Senderek J et al. (2000) Charcot–Marie–Tooth neuropathy type 2 and P0 point mutations: two novel amino acid substitutions (Asp61Gly; Tyr119Cys) and a possible “hotspot” on Thr124Met. Brain Pathol 10: 235–248

    CAS  PubMed  Google Scholar 

  53. Hanemann CO et al. (2001) Axon damage in CMT due to mutation in myelin protein P0. Neuromuscul Disord 11: 753–756

    CAS  PubMed  Google Scholar 

  54. Li J et al. (2006) Major myelin protein gene (P0) mutation causes a novel form of axonal degeneration. J Comp Neurol 498: 252–265

    CAS  PubMed  Google Scholar 

  55. Lappe-Siefke C et al. (2003) Disruption of Cnp1 uncouples oligodendroglial functions in axonal support and myelination. Nat Genet 33: 366–374

    CAS  PubMed  Google Scholar 

  56. Hahn AF et al. (1990) X-linked dominant hereditary motor and sensory neuropathy. Brain 113: 1511–1525

    PubMed  Google Scholar 

  57. Silander K et al. (1998) Spectrum of mutations in Finnish patients with Charcot–Marie–Tooth disease and related neuropathies. Hum Mutat 12: 59–68

    CAS  PubMed  Google Scholar 

  58. Numakura C et al. (2002) Molecular analysis in Japanese patients with Charcot–Marie–Tooth disease: DGGE analysis for PMP22, MPZ, and Cx32/GJB1 mutations. Hum Mutat 20: 392–398

    CAS  PubMed  Google Scholar 

  59. Bergoffen J et al. (1993) Connexin mutations in X-linked Charcot–Marie–Tooth disease. Science 262: 2039–2042

    CAS  PubMed  Google Scholar 

  60. Nicholson GA et al. (1998) Efficient neurophysiologic selection of X-linked Charcot–Marie–Tooth families: ten novel mutations. Neurology 51: 1412–1416

    CAS  PubMed  Google Scholar 

  61. Harding AE and Thomas PK (1980) Genetic aspects of hereditary motor and sensory neuropathy (types I and II). J Med Genet 17: 329–336

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Harding AE and Thomas PK (1980) The clinical features of hereditary motor and sensory neuropathy types I and II. Brain 103: 259–280

    CAS  PubMed  Google Scholar 

  63. Hahn AF et al. (1999) Genotype/phenotype correlations in X-linked dominant Charcot–Marie–Tooth disease. Ann N Y Acad Sci 883: 366–382

    CAS  PubMed  Google Scholar 

  64. Nicholson G and Corbett A (1996) Slowing of central conduction in X-linked Charcot–Marie–Tooth neuropathy shown by brain stem auditory evoked responses. J Neurol Neurosurg Psychiatry 61: 43–46

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Senderek J et al. (1999) X-linked dominant Charcot–Marie–Tooth neuropathy: clinical, electrophysiological, and morphological phenotype in four families with different connexin32 mutations. J Neurol Sci 167: 90–101

    CAS  PubMed  Google Scholar 

  66. Hanemann CO et al. (2003) Transient, recurrent, white matter lesions in X-linked Charcot–Marie–Tooth disease with novel connexin 32 mutation. Arch Neurol 60: 605–609

    PubMed  Google Scholar 

  67. Kleopa KA and Scherer SS (2006) Molecular genetics of X-linked Charcot–Marie–Tooth disease. Neuromolecular Med 8: 107–122

    CAS  PubMed  Google Scholar 

  68. Nelles E et al. (1996) Defective propagation of signals generated by sympathetic nerve stimulation in the liver of connexin32-deficient mice. Proc Natl Acad Sci USA 93: 9565–9570

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Anzini P et al. (1997) Structural abnormalities and deficient maintenance of peripheral nerve myelin in mice lacking the gap junction protein connexin 32. J Neurosci 17: 4545–4551

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Scherer SS et al. (1998) Connexin32-null mice develop demyelinating peripheral neuropathy. Glia 24: 8–20

    CAS  PubMed  Google Scholar 

  71. Kobsar I et al. (2005) Evidence for macrophage-mediated myelin disruption in an animal model for Charcot–Marie–Tooth neuropathy type 1A. J Neurosci Res 81: 857–864

    CAS  PubMed  Google Scholar 

  72. Scherer SS et al. (1995) Connexin32 is a myelin-related protein in the PNS and CNS. J Neurosci 15: 8281–8294

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Balice-Gordon RJ et al. (1998) Functional gap junctions in the Schwann cell myelin sheath. J Cell Biol 142: 1095–1104

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Yum SW et al. (2002) Diverse trafficking abnormalities of connexin32 mutants causing CMTX. Neurobiol Dis 11: 43–52

    CAS  PubMed  Google Scholar 

  75. Dubourg O et al. (2006) Autosomal-recessive forms of demyelinating Charcot–Marie–Tooth disease. Neuromolecular Med 8: 75–86

    CAS  PubMed  Google Scholar 

  76. Saifi GM et al. (2005) SIMPLE mutations in Charcot–Marie–Tooth disease and the potential role of its protein product in protein degradation. Hum Mutat 25: 372–383

    CAS  PubMed  Google Scholar 

  77. Senderek J et al. (2003) Mutations in a gene encoding a novel SH3/TPR domain protein cause autosomal recessive Charcot–Marie–Tooth type 4C neuropathy. Am J Hum Genet 73: 1106–1119

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Sherman DL et al. (2001) Specific disruption of a Schwann cell dystrophin-related protein complex in a demyelinating neuropathy. Neuron 30: 677–687

    CAS  PubMed  Google Scholar 

  79. Takashima H (2006) Molecular genetics of inherited neuropathies [Japanese]. Rinsho Shinkeigaku 46: 1–18

    PubMed  Google Scholar 

  80. Bolino A et al. (2000) Genetic refinement and physical mapping of the CMT4B gene on chromosome 11q22. Genomics 63: 271–278

    CAS  PubMed  Google Scholar 

  81. Berger P et al. (2002) Loss of phosphatase activity in myotubularin-related protein 2 is associated with Charcot–Marie–Tooth disease type 4B1. Hum Mol Genet 11: 1569–79

    CAS  PubMed  Google Scholar 

  82. Senderek J et al. (2003) Mutation of the SBF2 gene, encoding a novel member of the myotubularin family, in Charcot–Marie–Tooth neuropathy type 4B2/11p15. Hum Mol Genet 12: 349–356

    CAS  PubMed  Google Scholar 

  83. Baxter RV et al. (2002) Ganglioside-induced differentiation-associated protein-1 is mutant in Charcot–Marie–Tooth disease type 4A/8q21. Nat Genet 30: 21–22

    CAS  PubMed  Google Scholar 

  84. Cuesta A et al. (2002) The gene encoding ganglioside-induced differentiation-associated protein 1 is mutated in axonal Charcot–Marie–Tooth type 4A disease. Nat Genet 30: 22–25

    CAS  PubMed  Google Scholar 

  85. Niemann A et al. (2005) Ganglioside-induced differentiation associated protein 1 is a regulator of the mitochondrial network: new implications for Charcot–Marie–Tooth disease. J Cell Biol 170: 1067–1078

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Züchner S et al. (2004) Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot–Marie–Tooth neuropathy type 2A. Nat Genet 36: 449–451

    PubMed  Google Scholar 

  87. Warner LE et al. (1998) Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies. Nat Genet 18: 382–384

    CAS  PubMed  Google Scholar 

  88. Joseph LJ et al. (1988) Molecular cloning, sequencing, and mapping of EGR2, a human early growth response gene encoding a protein with “zinc-binding finger” structure. Proc Natl Acad Sci USA 85: 7164–7168

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Leblanc SE et al. (2005) Regulation of cholesterol/lipid biosynthetic genes by Egr2/Krox20 during peripheral nerve myelination. J Neurochem 93: 737–748

    CAS  PubMed  Google Scholar 

  90. Topilko P et al. (1994) Krox-20 controls myelination in the peripheral nervous system. Nature 371: 796–799

    CAS  PubMed  Google Scholar 

  91. Inoue K et al. (2002) Congenital hypomyelinating neuropathy, central dysmyelination, and Waardenburg–Hirschsprung disease: phenotypes linked by SOX10 mutation. Ann Neurol 52: 836–842

    CAS  PubMed  Google Scholar 

  92. LeBlanc SE et al. (2006) Direct regulation of myelin protein zero expression by the Egr2 transactivator. J Biol Chem 281: 5453–5460

    CAS  PubMed  Google Scholar 

  93. Jordanova A et al. (2006) Disrupted function and axonal distribution of mutant tyrosyl-tRNA synthetase in dominant intermediate Charcot–Marie–Tooth neuropathy. Nat Genet 38: 197–202

    CAS  PubMed  Google Scholar 

  94. Antonellis A et al. (2003) Glycyl tRNA synthetase mutations in Charcot–Marie–Tooth disease type 2D and distal spinal muscular atrophy type V. Am J Hum Genet 72: 1293–1299

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Schiffmann R and van der Knaap MS (2004) The latest on leukodystrophies. Curr Opin Neurol 17: 187–192

    CAS  PubMed  Google Scholar 

  96. Schiffmann R and Elroy-Stein O (2006) Childhood ataxia with CNS hypomyelination/vanishing white matter disease—a common leukodystrophy caused by abnormal control of protein synthesis. Mol Genet Metab 88: 7–15

    CAS  PubMed  Google Scholar 

  97. Chen S et al. (2003) Disruption of ErbB receptor signaling in adult non-myelinating Schwann cells causes progressive sensory loss. Nat Neurosci 6: 1186–1193

    CAS  PubMed  Google Scholar 

  98. Meyer Zu Horste G et al. (2007) Antiprogesterone therapy uncouples axonal loss from demyelination in a transgenic rat model of CMT1A neuropathy. Ann Neurol 61: 61–72

    CAS  PubMed  Google Scholar 

  99. Griffiths I et al. (1998) Axonal swellings and degeneration in mice lacking the major proteolipid of myelin. Science 280: 1610–1613

    CAS  PubMed  Google Scholar 

  100. Chen H and Chan DC (2006) Critical dependence of neurons on mitochondrial dynamics. Curr Opin Cell Biol 18: 453–459

    CAS  PubMed  Google Scholar 

  101. Pop-Busui R et al. (2006) Diabetic neuropathy and oxidative stress. Diabetes Metab Res Rev 22: 257–273

    CAS  PubMed  Google Scholar 

  102. Shy ME (2006) Therapeutic strategies for the inherited neuropathies. Neuromolecular Med 8: 255–278

    CAS  PubMed  Google Scholar 

  103. Shy ME et al. (2005) Reliability and validity of the CMT neuropathy score as a measure of disability. Neurology 64: 1209–1214

    CAS  PubMed  Google Scholar 

  104. Sahenk Z et al. (2005) NT-3 promotes nerve regeneration and sensory improvement in CMT1A mouse models and in patients. Neurology 65: 681–689

    CAS  PubMed  Google Scholar 

  105. Hassan K et al. (2003) Effect of erythropoietin therapy on polyneuropathy in predialytic patients. J Nephrol 16: 121–125

    CAS  PubMed  Google Scholar 

  106. Keswani SC et al. (2004) Erythropoietin is neuroprotective in models of HIV sensory neuropathy. Neurosci Lett 371: 102–105

    CAS  PubMed  Google Scholar 

  107. Sugawa M et al. (2002) Effects of erythropoietin on glial cell development; oligodendrocyte maturation and astrocyte proliferation. Neurosci Res 44: 391–403

    CAS  PubMed  Google Scholar 

  108. Scarlato M et al. (2005) Polyneuropathy in POEMS syndrome: role of angiogenic factors in the pathogenesis. Brain 128: 1911–1920

    PubMed  Google Scholar 

Download references

Acknowledgements

We thank the unknown reviewers of this manuscript for helpful suggestions, and apologize to our colleagues when publications could not be cited owing to space limitations. Work in the authors' laboratory was generously supported by grants from the Deutsche Forschungsgemeinschaft (Center for Molecular Biology of the Brain), Hertie Institute for Multiple Sclerosis Research, the US National Multiple Sclerosis Society, European Union (FP6), and private foundations (Del Marmol Fund, Liley Fund).

Author information

Authors and Affiliations

  1. K-A Nave is the Director of the Department of Neurogenetics and MW Sereda is a Neurologist in the Departments of Neurology and Clinical Neurophysiology, University of Göttingen, and Junior Group Leader at the Max Planck Institute of Experimental Medicine. H Ehrenreich is Professor of Psychiatry and Neurology at the Max Planck Institute of Experimental Medicine and the University of Göttingen, Göttingen, Germany.,

    Klaus-Armin Nave, Michael W Sereda & Hannelore Ehrenreich

Authors
  1. Klaus-Armin Nave
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael W Sereda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hannelore Ehrenreich
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Klaus-Armin Nave.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nave, KA., Sereda, M. & Ehrenreich, H. Mechanisms of Disease: inherited demyelinating neuropathies—from basic to clinical research. Nat Rev Neurol 3, 453–464 (2007). https://doi.org/10.1038/ncpneuro0583

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncpneuro0583

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing