Semaphorins pp 189-205 | Cite as

Semaphorins and Neurodegenerative Disorders

Chapter

Abstract

Neurodegenerative disorders are characterized by progressive dysfunction or death and structural abnormalities of neurons. A number of diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS) that result from neurodegenerative processes are included in this category. Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). However, accumulating evidence indicates that a neurodegenerative process participates in the pathogenesis, particularly in the progressive stage of the disease. Although various causes of neurodegenerative disorders, including genetic mutations, protein abnormalities, and inflammation, have been reported, changes in neural connectivity, loss of synaptic contacts and activity, and inflammatory reactions in glial cells are common features of these disorders. It has been suggested that aberrant semaphorin expression may result in altered neuronal connectivity or synaptic function and inflammation associated with a number of degenerative neuronal disorders. This role of semaphorins has been currently suggested in the pathogenesis of AD, ALS, and MS (Table 10.1).

Keywords

Alzheimer’s disease Parkinson’s disease Amyotrophic lateral sclerosis Multiple sclerosis Experimental autoimmune encephalomyelitis 
This is a preview of subscription content, log in to check access.

References

  1. Adams RH, Betz H et al (1996) A novel class of murine semaphorins with homology to thrombospondin is differentially expressed during early embryogenesis. Mech Dev 57:33–45CrossRefPubMedGoogle Scholar
  2. Artigiani S, Conrotto P et al (2004) Plexin-B3 is a functional receptor for semaphorin 5A. EMBO Rep 5:710–714CrossRefPubMedCentralPubMedGoogle Scholar
  3. Bakker ABH, Hoek RM et al (2000) DAP12-deficient mice fail to develop autoimmunity due to impaired antigen priming. Immunity 13:345–353CrossRefPubMedGoogle Scholar
  4. Beghi E, Logroscino G et al (2006) The epidemiology of ALS and the role of population-based registries. Biochim Biophys Acta 1762:1150–1157CrossRefPubMedGoogle Scholar
  5. Bettelli E, Oukka M et al (2007) T(H)-17 cells in the circle of immunity and autoimmunity. Nat Immunol 8:345–350CrossRefPubMedGoogle Scholar
  6. Bialecka M, Kurzawski M et al (2006) Polymorphism in semaphorin 5A (Sema5A) gene is not a marker of Parkinson’s disease risk. Neurosci Lett 399:121–123CrossRefPubMedGoogle Scholar
  7. Bjartmar C, Kidd G et al (2000) Neurological disability correlates with spinal cord axonal loss and reduced N-acetyl aspartate in chronic multiple sclerosis patients. Ann Neurol 48:893–901CrossRefPubMedGoogle Scholar
  8. Blennow K, de Leon MJ et al (2006) Alzheimer’s disease. Lancet 368:387–403CrossRefPubMedGoogle Scholar
  9. Braak H, Braak E (1991) Neuropathological staging of Alzheimer-related changes. Acta Neuropathol 82:239–259CrossRefPubMedGoogle Scholar
  10. Calne DB, Snow BJ et al (1992) Criteria for diagnosing Parkinson’s disease. Ann Neurol 32(Suppl):S125–S127CrossRefPubMedGoogle Scholar
  11. Chun W, Johnson GV (2007) The role of tau phosphorylation and cleavage in neuronal cell death. Front Biosci 12:733–756CrossRefPubMedGoogle Scholar
  12. Clarimon J, Scholz S et al (2006) Conflicting results regarding the semaphorin gene (SEMA5A) and the risk for Parkinson disease. Am J Hum Genet 78:1082–1084, author reply 1092–1094CrossRefPubMedCentralPubMedGoogle Scholar
  13. Compston A, Coles A (2002) Multiple sclerosis. Lancet 359:1221–1231CrossRefPubMedGoogle Scholar
  14. Cudkowicz ME, McKenna-Yasek D et al (1997) Epidemiology of mutations in superoxide dismutase in amyotrophic lateral sclerosis. Ann Neurol 41:210–221CrossRefPubMedGoogle Scholar
  15. De Winter F, Vo T et al (2006) The expression of the chemorepellent semaphorin 3A is selectively induced in terminal Schwann cells of a subset of neuromuscular synapses that display limited anatomical plasticity and enhanced vulnerability in motor neuron disease. Mol Cell Neurosci 32:102–117CrossRefPubMedGoogle Scholar
  16. Elbaz A, Nelson LM et al (2006) Lack of replication of thirteen single-nucleotide polymorphisms implicated in Parkinson’s disease: a large-scale international study. Lancet Neurol 5:917–923CrossRefPubMedCentralPubMedGoogle Scholar
  17. Fischer LR, Culver DG et al (2004) Amyotrophic lateral sclerosis is a distal axonopathy: evidence in mice and man. Exp Neurol 185:232–240CrossRefPubMedGoogle Scholar
  18. Frey D, Schneider C et al (2000) Early and selective loss of neuromuscular synapse subtypes with low sprouting competence in motoneuron diseases. J Neurosci 20:2534–2542PubMedGoogle Scholar
  19. Fugger L, Friese MA et al (2009) From genes to function: the next challenge to understanding multiple sclerosis. Nat Rev Immunol 9:408–417CrossRefPubMedGoogle Scholar
  20. Fukata Y, Itoh TJ et al (2002) CRMP-2 binds to tubulin heterodimers to promote microtubule assembly. Nat Cell Biol 4:583–591PubMedGoogle Scholar
  21. Giraudon P, Vincent P et al (2004) Semaphorin CD100 from activated T lymphocytes induces process extension collapse in oligodendrocytes and death of immature neural cells. J Immunol 172:1246–1255CrossRefPubMedGoogle Scholar
  22. Goedert M, Spillantini MG et al (1991) Tau proteins and neurofibrillary degeneration. Brain Pathol 1:279–286CrossRefPubMedGoogle Scholar
  23. Goldberg JL, Vargas ME et al (2004) An oligodendrocyte lineage-specific semaphorin, Sema5A, inhibits axon growth by retinal ganglion cells. J Neurosci 24:4989–4999CrossRefPubMedGoogle Scholar
  24. Good PF, Alapat D et al (2004) A role for semaphorin 3A signaling in the degeneration of hippocampal neurons during Alzheimer’s disease. J Neurochem 91:716–736CrossRefPubMedGoogle Scholar
  25. Gurney ME, Pu H et al (1994) Motor neuron degeneration in mice that express a human Cu, Zn superoxide dismutase mutation. Science 264:1772–1775CrossRefPubMedGoogle Scholar
  26. Haass C, Selkoe DJ (2007) Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid beta-peptide. Nat Rev Mol Cell Biol 8:101–112CrossRefPubMedGoogle Scholar
  27. Hafler DA, Compston A et al (2007) Risk alleles for multiple sclerosis identified by a genome-wide study. N Engl J Med 357:851–862CrossRefPubMedGoogle Scholar
  28. Hansen RA, Gartlehner G et al (2008) Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer’s disease: a systematic review and meta-analysis. Clin Interv Aging 3:211–225PubMedCentralPubMedGoogle Scholar
  29. Hardy J, Allsop D (1991) Amyloid deposition as the central event in the aetiology of Alzheimer’s disease. Trends Pharmacol Sci 12:383–388CrossRefPubMedGoogle Scholar
  30. Horner RD, Kamins KG et al (2003) Occurrence of amyotrophic lateral sclerosis among Gulf War veterans. Neurology 61:742–749CrossRefPubMedGoogle Scholar
  31. Hsiao K, Chapman P et al (1996) Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science 274:99–102CrossRefPubMedGoogle Scholar
  32. Iqbal K, Alonso Adel C et al (2005) Tau pathology in Alzheimer disease and other tauopathies. Biochim Biophys Acta 1739:198–210CrossRefPubMedGoogle Scholar
  33. Kumanogoh A, Watanabe C et al (2000) Identification of CD72 as a lymphocyte receptor for the class IV semaphorin CD100: a novel mechanism for regulating B cell signaling. Immunity 13:621–631CrossRefPubMedGoogle Scholar
  34. Kumanogoh A, Marukawa S et al (2002a) Class IV semaphorin Sema4A enhances T-cell activation and interacts with Tim-2. Nature (Lond) 419:629–633CrossRefGoogle Scholar
  35. Kumanogoh A, Suzuki K et al (2002b) Requirement for the lymphocyte semaphorin, CD100, in the induction of antigen-specific T cells and the maturation of dendritic cells. J Immunol 169:1175–1181CrossRefPubMedGoogle Scholar
  36. Kumanogoh A, Shikina T et al (2005) Nonredundant roles of Sema4A in the immune system: defective T cell priming and Th1/Th2 regulation in Sema4A-deficient mice. Immunity 22:305–316CrossRefPubMedGoogle Scholar
  37. Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452CrossRefPubMedGoogle Scholar
  38. Lesnick TG, Papapetropoulos S et al (2007) A genomic pathway approach to a complex disease: axon guidance and Parkinson disease. PLoS Genet 3:e98CrossRefPubMedCentralPubMedGoogle Scholar
  39. Lesnick TG, Sorenson EJ et al (2008) Beyond Parkinson disease: amyotrophic lateral sclerosis and the axon guidance pathway. PLoS One 3:e1449CrossRefPubMedCentralPubMedGoogle Scholar
  40. Lincoln MR, Montpetit A et al (2005) A predominant role for the HLA class II region in the association of the MHC region with multiple sclerosis. Nat Genet 37:1108–1112CrossRefPubMedGoogle Scholar
  41. Lucchinetti C, Bruck W et al (2000) Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 47:707–717CrossRefPubMedGoogle Scholar
  42. Lucchinetti CF, Bruck W et al (2004) Evidence for pathogenic heterogeneity in multiple sclerosis. Ann Neurol 56:308CrossRefPubMedGoogle Scholar
  43. Makino N, Toyofuku T et al (2008) Involvement of Sema4A in the progression of experimental autoimmune myocarditis. FEBS Lett 582:3935–3940CrossRefPubMedGoogle Scholar
  44. Maraganore DM, de Andrade M et al (2005) High-resolution whole-genome association study of Parkinson disease. Am J Hum Genet 77:685–693CrossRefPubMedCentralPubMedGoogle Scholar
  45. McFarland HF, Martin R (2007) Multiple sclerosis: a complicated picture of autoimmunity. Nat Immunol 8:913–919CrossRefPubMedGoogle Scholar
  46. Mitchell JD, Borasio GD (2007) Amyotrophic lateral sclerosis. Lancet 369:2031–2041CrossRefPubMedGoogle Scholar
  47. Mix E, Meyer-Rienecker H et al (2008) Animal models of multiple sclerosis for the development and validation of novel therapies – potential and limitations. J Neurol 255(Suppl 6):7–14CrossRefPubMedGoogle Scholar
  48. Molsa PK, Marttila RJ et al (1986) Survival and cause of death in Alzheimer’s disease and multi-infarct dementia. Acta Neurol Scand 74:103–107CrossRefPubMedGoogle Scholar
  49. Molsa PK, Marttila RJ et al (1995) Long-term survival and predictors of mortality in Alzheimer’s disease and multi-infarct dementia. Acta Neurol Scand 91:159–164CrossRefPubMedGoogle Scholar
  50. Mudher A, Lovestone S (2002) Alzheimer’s disease: -do tauists and baptists finally shake hands? Trends Neurosci 25:22–26CrossRefPubMedGoogle Scholar
  51. Nakatsuji Y, Okuno T et al (2012) Elevation of Sema4A implicates Th cell skewing and the efficacy of IFN-beta therapy in multiple sclerosis. J Immunol 188:4858–4865CrossRefPubMedGoogle Scholar
  52. Nichols WC, Pankratz N et al (2005) Genetic screening for a single common LRRK2 mutation in familial Parkinson’s disease. Lancet 365:410–412PubMedGoogle Scholar
  53. Noseworthy JH, Lucchinetti C et al (2000) Multiple sclerosis. N Engl J Med 343:938–952CrossRefPubMedGoogle Scholar
  54. Okuno T, Nakatsuji Y et al (2010) Roles of Sema4D–plexin-B1 interactions in the central nervous system for pathogenesis of experimental autoimmune encephalomyelitis. J Immunol 184:1499–1506CrossRefPubMedGoogle Scholar
  55. Oster SF, Bodeker MO et al (2003) Invariant Sema5A inhibition serves an ensheathing function during optic nerve development. Development (Camb) 130:775–784CrossRefGoogle Scholar
  56. Pasinelli P, Brown RH (2006) Molecular biology of amyotrophic lateral sclerosis: insights from genetics. Nat Rev Neurosci 7:710–723CrossRefPubMedGoogle Scholar
  57. Pasterkamp RJ, Giger RJ (2009) Semaphorin function in neural plasticity and disease. Curr Opin Neurobiol 19:263–274CrossRefPubMedCentralPubMedGoogle Scholar
  58. Pasterkamp RJ, Peschon JJ et al (2003) Semaphorin 7A promotes axon outgrowth through integrins and MAPKs. Nature (Lond) 424:398–405CrossRefGoogle Scholar
  59. Petratos S, Li QX et al (2008) The beta-amyloid protein of Alzheimer’s disease increases neuronal CRMP-2 phosphorylation by a Rho-GTP mechanism. Brain 131:90–108CrossRefPubMedGoogle Scholar
  60. Piaton G, Aigrot MS et al (2011) Class 3 semaphorins influence oligodendrocyte precursor recruitment and remyelination in adult central nervous system. Brain 134:1156–1167CrossRefPubMedGoogle Scholar
  61. Pineda D, García B et al (2005) Semaphorin5A expression in the developing chick telencephalon. Brain Res Bull 66:436–440CrossRefPubMedGoogle Scholar
  62. Pinter MJ, Waldeck RF et al (1995) Motor unit behavior in canine motor neuron disease. J Neurosci 15:3447–3457PubMedGoogle Scholar
  63. Polymeropoulos MH, Lavedan C et al (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science 276:2045–2047CrossRefPubMedGoogle Scholar
  64. Pradat PF, Bruneteau G et al (2007) Muscle Nogo-A expression is a prognostic marker in lower motor neuron syndromes. Ann Neurol 62:15–20CrossRefPubMedGoogle Scholar
  65. Price JL, Davis PB et al (1991) The distribution of tangles, plaques and related immunohistochemical markers in healthy aging and Alzheimer’s disease. Neurobiol Aging 12:295–312CrossRefPubMedGoogle Scholar
  66. Pun S, Santos AF et al (2006) Selective vulnerability and pruning of phasic motoneuron axons in motoneuron disease alleviated by CNTF. Nat Neurosci 9:408–419CrossRefPubMedGoogle Scholar
  67. Radunović A, Mitsumoto H et al (2007) Clinical care of patients with amyotrophic lateral sclerosis. Lancet Neurol 6:913–925CrossRefPubMedGoogle Scholar
  68. Rosen DR, Siddique T et al (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature (Lond) 362:59–62CrossRefGoogle Scholar
  69. Rowland LP (1998) Diagnosis of amyotrophic lateral sclerosis. J Neurol Sci 160(Suppl 1):S6–S24CrossRefPubMedGoogle Scholar
  70. Rowland LP, Shneider NA (2001) Amyotrophic lateral sclerosis. N Engl J Med 344:1688–1700CrossRefPubMedGoogle Scholar
  71. Shaw PJ (2005) Molecular and cellular pathways of neurodegeneration in motor neurone disease. J Neurol Neurosurg Psychiatry 76:1046–1057CrossRefPubMedCentralPubMedGoogle Scholar
  72. Siddique N, Siddique T (2008) Genetics of amyotrophic lateral sclerosis. Phys Med Rehabil Clin N Am 19:429–439, viiCrossRefPubMedCentralPubMedGoogle Scholar
  73. Sospedra M, Martin R (2005) Immunology of multiple sclerosis. Annu Rev Immunol 23:683–747CrossRefPubMedGoogle Scholar
  74. Steinman L (2004) Elaborate interactions between the immune and nervous systems. Nat Immunol 5:575–581CrossRefPubMedGoogle Scholar
  75. Stromnes IM, Cerretti LM et al (2008) Differential regulation of central nervous system autoimmunity by T(H)1 and T(H)17 cells. Nat Med 14:337–342CrossRefPubMedCentralPubMedGoogle Scholar
  76. Sutedja NA, Veldink JH et al (2007) Lifetime occupation, education, smoking, and risk of ALS. Neurology 69:1508–1514CrossRefPubMedGoogle Scholar
  77. Suzuki K, Okuno T et al (2007) Semaphorin 7A initiates T-cell-mediated inflammatory responses through alpha1beta1 integrin. Nature (Lond) 446:680–684CrossRefGoogle Scholar
  78. Syed YA, Hand E et al (2011) Inhibition of CNS remyelination by the presence of semaphorin 3A. J Neurosci 31:3719–3728CrossRefPubMedGoogle Scholar
  79. Takamatsu H, Takegahara N et al (2010) Semaphorins guide the entry of dendritic cells into the lymphatics by activating myosin II. Nat Immunol 11:594–600CrossRefPubMedCentralPubMedGoogle Scholar
  80. Takegahara N, Takamatsu H et al (2006) Plexin-A1 and its interaction with DAP12 in immune responses and bone homeostasis. Nat Cell Biol 8:615–622CrossRefPubMedGoogle Scholar
  81. Tamagnone L, Artigiani S et al (1999) Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates. Cell 99:71–80CrossRefPubMedGoogle Scholar
  82. Tiraboschi P, Hansen LA et al (2004) The importance of neuritic plaques and tangles to the development and evolution of AD. Neurology 62:1984–1989CrossRefPubMedGoogle Scholar
  83. Toyofuku T, Zhang H et al (2004) Dual roles of Sema6D in cardiac morphogenesis through region-specific association of its receptor, Plexin-A1, with off-track and vascular endothelial growth factor receptor type 2. Genes Dev 18:435–447CrossRefPubMedCentralPubMedGoogle Scholar
  84. Trapp BD, Nave KA (2008) Multiple sclerosis: an immune or neurodegenerative disorder? Annu Rev Neurosci 31:247–269CrossRefPubMedGoogle Scholar
  85. Trapp BD, Peterson J et al (1998) Axonal transection in the lesions of multiple sclerosis. N Engl J Med 338:278–285CrossRefPubMedGoogle Scholar
  86. Tzartos JS, Friese MA et al (2008) Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis. Am J Pathol 172:146–155CrossRefPubMedCentralPubMedGoogle Scholar
  87. Uchida Y, Ohshima T et al (2005) Semaphorin3A signalling is mediated via sequential Cdk5 and GSK3beta phosphorylation of CRMP2: implication of common phosphorylating mechanism underlying axon guidance and Alzheimer’s disease. Genes Cells 10:165–179CrossRefPubMedGoogle Scholar
  88. Valente EM, Bentivoglio AR et al (2001) Localization of a novel locus for autosomal recessive early-onset parkinsonism, PARK6, on human chromosome 1p35-p36. Am J Hum Genet 68:895–900CrossRefPubMedCentralPubMedGoogle Scholar
  89. Van Deerlin VM, Leverenz JB et al (2008) TARDBP mutations in amyotrophic lateral sclerosis with TDP-43 neuropathology: a genetic and histopathological analysis. Lancet Neurol 7:409–416CrossRefPubMedCentralPubMedGoogle Scholar
  90. Waldemar G, Dubois B et al (2007) Recommendations for the diagnosis and management of Alzheimer’s disease and other disorders associated with dementia: EFNS guideline. Eur J Neurol 14:e1–e26CrossRefPubMedGoogle Scholar
  91. Wang SJ, Wang KY et al (2004) Mechanisms underlying the riluzole inhibition of glutamate release from rat cerebral cortex nerve terminals (synaptosomes). Neuroscience 125:191–201CrossRefPubMedGoogle Scholar
  92. Waring SC, Rosenberg RN (2008) Genome-wide association studies in Alzheimer disease. Arch Neurol 65:329–334CrossRefPubMedGoogle Scholar
  93. Wenk GL (2003) Neuropathologic changes in Alzheimer’s disease. J Clin Psychiatry 64(Suppl 9):7–10PubMedGoogle Scholar
  94. Williams A, Piaton G et al (2007) Semaphorin 3A and 3F: key players in myelin repair in multiple sclerosis? Brain 130:2554–2565CrossRefPubMedGoogle Scholar
  95. Wong PC, Pardo CA et al (1995) An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria. Neuron 14:1105–1116CrossRefPubMedGoogle Scholar
  96. Yokoseki A, Shiga A et al (2008) TDP-43 mutation in familial amyotrophic lateral sclerosis. Ann Neurol 63:538–542CrossRefPubMedGoogle Scholar
  97. Yoshimura T, Kawano Y et al (2005) GSK-3β regulates phosphorylation of CRMP-2 and neuronal polarity. Cell 120:137–149CrossRefPubMedGoogle Scholar

Copyright information

© Springer Japan 2015

Authors and Affiliations

  1. 1.Department of NeurologyOsaka University Graduate School of MedicineOsakaJapan

Personalised recommendations