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Functional Roles of Gangliosides in Neurodevelopment: An Overview of Recent Advances

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Abstract

Gangliosides are sialic acid-containing glycosphingolipids that are most abundant in the nervous system. They are localized primarily in the outer leaflets of plasma membranes and participated in cell–cell recognition, adhesion, and signal transduction and are integral components of cell surface microdomains or lipid rafts along with proteins, sphingomyelin and cholesterol. Ganglioside-rich lipid rafts play an important role in signaling events affecting neural development and the pathogenesis of certain diseases. Disruption of gangloside synthase genes in mice induces developmental defects and neural degeneration. Targeting ganglioside metabolism may represent a novel therapeutic strategy for intervention in certain diseases. In this review, we focus on recent advances on metabolic and functional studies of gangliosides in normal brain development and in certain neurological disorders.

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Abbreviations

GSL:

Glycosphingolipid

CNS:

Central nervous system

PNS:

Peripheral nervous system

GT:

Glycosyltransferase

GEM:

GSL-enriched microdomain

NMJ:

Neuromuscular junction

Tag:

Transgenic mouse

WT:

Wild-type mouse

AD:

Alzheimer’s disease

HD:

Hungtinton’s disease

PD:

Parkinson’s disease

NSC:

Neural stem cell

NPC:

Neural progenitor cell

GBS:

Guillain-Barré syndrome

References

  1. Yu RK, Nakatani Y, Yanagisawa M (2009) The role of glycosphingolipid metabolism in the developing brain. J Lipid Res 50(Suppl):S440–S445

    Article  PubMed  CAS  Google Scholar 

  2. Yu RK, Yanagisawa M, Ariga T (2007) Glycosphingolipid structures. In: Kamerling JP (ed) Comprehensive Glycoscience. Elsevier, Oxford, pp 73–122

    Chapter  Google Scholar 

  3. Furukawa K, Ohmi Y, Ohkawa Y, Tokuda N, Kondo Y, Tajima O (2011) Regulatory mechanisms of nervous systems with glycosphingolipids. Neurochem Res 36:1578–1586

    Article  PubMed  CAS  Google Scholar 

  4. Anderson RG (1998) The caveolae membrane system. Annu Rev Biochem 67:199–225

    Article  PubMed  CAS  Google Scholar 

  5. Simons K, Ehehalt R (2002) Cholesterol, lipid rafts, and disease. J Clin Invest 110:597–603

    PubMed  CAS  Google Scholar 

  6. Hakomori S, Handa K, Iwabuchi K, Yamamura S, Prinetti A (1998) New insights in glycosphingolipid function: “glycosignaling domain,” a cell surface assembly of glycosphingolipids with signal transducer molecules, involved in cell adhesion coupled with signaling. Glycobiology 8:xi–xix

    Google Scholar 

  7. Ledeen RW, Wu G (2008) Nuclear sphingolipids: metabolism and signaling. J Lipid Res 49:1176–1186

    Article  PubMed  CAS  Google Scholar 

  8. Nakamura K, Inagaki F, Tamai Y (1988) A novel ganglioside in dogfish brain. Occurrence of a trisialoganglioside with a sialic acid linked to N-acetylgalactosamine. J Biol Chem 263:9896–9900

    PubMed  CAS  Google Scholar 

  9. Maccioni HJ (2007) Glycosylation of glycolipids in the golgi complex. J Neurochem 103(Suppl 1):81–90

    Article  PubMed  CAS  Google Scholar 

  10. Ngamukote S, Yanagisawa M, Ariga T, Ando S, Yu RK (2007) Developmental changes of glycosphingolipids and expression of glycogenes in mouse brains. J Neurochem 103:2327–2341

    Article  PubMed  CAS  Google Scholar 

  11. Yu RK, Macala LJ, Taki T, Weinfield HM, Yu FS (1988) Developmental changes in ganglioside composition and synthesis in embryonic rat brain. J Neurochem 50:1825–1829

    Article  PubMed  CAS  Google Scholar 

  12. Ishii A, Ikeda T, Hitoshi S et al (2007) Developmental changes in the expression of glycogenes and the content of N-glycans in the mouse cerebral cortex. Glycobiology 17:261–276

    Article  PubMed  CAS  Google Scholar 

  13. Yu RK, Ariga T, Yanagisawa M, Zeng G (2008) Gangliosides in the nervous system: Biosynthesis and degradation. In: Fraser-Reid B, Tatsuka K, Thiem J (eds) Glycoscience. Springer-Verlag, Berlin-Heiderberg, pp 1671–1695

    Chapter  Google Scholar 

  14. Suzuki Y, Yanagisawa M, Ariga T, Yu RK (2011) Histone acetylation-mediated glycosyltransferase gene regulation in mouse brain during development. J Neurochem 116:874–880

    Article  PubMed  CAS  Google Scholar 

  15. Yu RK, Bieberich E, Xia T, Zeng G (2004) Regulation of ganglioside biosynthesis in the nervous system. J Lipid Res 45:783–793

    Article  PubMed  CAS  Google Scholar 

  16. Fukumoto S, Miyazaki H, Goto G, Urano T, Furukawa K (1999) Expression cloning of mouse cDNA of CMP-NeuAc:Lactosylceramide alpha2,3-sialyltransferase, an enzyme that initiates the synthesis of gangliosides. J Biol Chem 274:9271–9276

    Article  PubMed  CAS  Google Scholar 

  17. Kono M, Takashima S, Liu H et al (1998) Molecular cloning and functional expression of a fifth-type alpha 2,3-sialyltransferase (mST3Gal V: GM3 synthase). Biochem Biophys Res Commun 253:170–175

    Article  PubMed  CAS  Google Scholar 

  18. Xia T, Zeng G, Gao L, Yu RK (2005) Sp1 and AP2 enhance promoter activity of the mouse GM3-synthase gene. Gene 351:109–118

    Article  PubMed  CAS  Google Scholar 

  19. Chung T-W, Choi H-J, Lee Y-C, Kim C-H (2005) Molecular mechanism for transcriptional activation of ganglioside GM3 synthase and its function in differentiation of HL-60 cells. Glycobiology 15:233–244

    Article  PubMed  CAS  Google Scholar 

  20. Kim S-W, Lee S-H, Kim K-S, Kim C-H, Choo Y-K, Lee Y-C (2002) Isolation and characterization of the promoter region of the human GM3 synthase gene. Biochim Biophys Acta 1578:84–89

    PubMed  CAS  Google Scholar 

  21. Zeng G, Gao L, Xia T, Tencomnao T, Yu RK (2003) Characterization of the 5′-flanking fragment of the human GM3-synthase gene. Biochim Biophys Acta 1625:30–35

    PubMed  CAS  Google Scholar 

  22. Zeng G, Gao L, Yu RK (1998) Isolation and functional analysis of the promoter of the rat CMP-NeuAc:GM3 alpha2,8 sialyltransferase gene 1. Biochim Biophys Acta 1397:126–130

    PubMed  CAS  Google Scholar 

  23. Takashima S, Kono M, Kurosawa N et al (2000) Genomic organization and transcriptional regulation of the mouse GD3 synthase gene (ST8Sia I): comparison of genomic organization of the mouse sialyltransferase genes. J Biochem (Tokyo) 128:1033–1043

    Article  CAS  Google Scholar 

  24. Furukawa K, Horie M, Okutomi K, Sugano S (2003) Isolation and functional analysis of the melanoma specific promoter region of human GD3 synthase gene. Biochim Biophys Acta 1627:71–78

    PubMed  CAS  Google Scholar 

  25. Furukawa K, Soejima H, Niikawa N, Shiku H (1996) Genomic organization and chromosomal assignment of the human beta1, 4-N-acetylgalactosaminyltransferase gene. Identification of multiple transcription units. J Biol Chem 271:20836–20844

    Article  PubMed  CAS  Google Scholar 

  26. Xia T, Gao L, Yu RK, Zeng G (2003) Characterization of the promoter and the transcription factors for the mouse UDP-Gal:betaGlcNAc beta1,3-galactosyltransferase gene. Gene 309:117–123

    Article  PubMed  CAS  Google Scholar 

  27. Ichikawa S, Ozawa K, Hirabayashi Y (1998) Molecular cloning and characterization of the mouse ceramide glucosyltransferase gene. Biochem Biophys Res Commun 253:707–711

    Article  PubMed  CAS  Google Scholar 

  28. Yu RK, Lee SH (1976) In vitro biosynthesis of sialosylgalactosylceramide (G7) by mouse brain microsomes. J Biol Chem 251:198–203

    PubMed  CAS  Google Scholar 

  29. Tencomnao T, Yu RK, Kapitonov D (2001) Characterization of the human UDP-galactose:ceramide galactosyltransferase gene promoter. Biochim Biophys Acta 1517:416–423

    PubMed  CAS  Google Scholar 

  30. Tencomnao T, Kapitonov D, Bieberich E, Yu RK (2004) Transcriptional regulation of the human UDP-galactose:ceramide galactosyltransferase (hCGT) gene expression: functional role of GC-box and CRE. Glycoconj J 20:339–351

    Article  PubMed  CAS  Google Scholar 

  31. Goldberg AD, Allis CD, Bernstein E (2007) Epigenetics: a landscape takes shape. Cell 128:635–638

    Article  PubMed  CAS  Google Scholar 

  32. Mohn F, Schübeler D (2009) Genetics and epigenetics: stability and plasticity during cellular differentiation. Trends Genet 25:129–136

    Article  PubMed  CAS  Google Scholar 

  33. Kizuka Y, Kitazume S, Yoshida M, Taniguchi N (2011) Brain-specific expression of N-acetylglucosaminyltransferase IX (GnT-IX) is regulated by epigenetic histone modifications. J Biol Chem 286:31875–31884

    Article  PubMed  CAS  Google Scholar 

  34. Bouvier JD, Seyfried TN (1989) Ganglioside composition of normal and mutant mouse embryos. J Neurochem 52:460–466

    Article  PubMed  CAS  Google Scholar 

  35. Nakatani Y, Yanagisawa M, Suzuki Y, Yu RK (2010) Characterization of GD3 ganglioside as a novel biomarker of mouse neural stem cells. Glycobiology 20:78–86

    Article  PubMed  CAS  Google Scholar 

  36. Bieberich E, MacKinnon S, Silva J, Yu RK (2001) Regulation of apoptosis during neuronal differentiation by ceramide and b-series complex gangliosides. J Biol Chem 276:44396–44404

    Article  PubMed  CAS  Google Scholar 

  37. Fang Y, Wu G, Xie X, Lu ZH, Ledeen RW (2000) Endogenous GM1 ganglioside of the plasma membrane promotes neuritogenesis by two mechanisms. Neurochem Res 25:931–940

    Article  PubMed  CAS  Google Scholar 

  38. Wu G, Fang Y, Lu ZH, Ledeen RW (1998) Induction of axon-like and dendrite-like processes in neuroblastoma cells. J Neurocytol 27:1–14

    Article  PubMed  CAS  Google Scholar 

  39. Wu G, Lu ZH, Xie X, Li L, Ledeen RW (2001) Mutant NG108-15 cells (NG-CR72) deficient in GM1 synthase respond aberrantly to axonogenic stimuli and are vulnerable to calcium-induced apoptosis: they are rescued with LIGA-20. J Neurochem 76:690–702

    Article  PubMed  CAS  Google Scholar 

  40. Simpson MA, Cross H, Proukakis C et al (2004) Infantile-onset symptomatic epilepsy syndrome caused by a homozygous loss-of-function mutation of GM3 synthase. Nat Genet 36:1225–1229

    Article  PubMed  CAS  Google Scholar 

  41. Proia RL (2003) Glycosphingolipid functions: insights from engineered mouse models. Philos Trans R Soc Lond B Biol Sci 358:879–883

    Article  PubMed  CAS  Google Scholar 

  42. Ohmi Y, Tajima O, Ohkawa Y, Mori A, Sugiura Y, Furukawa K (2009) Gangliosides play pivotal roles in the regulation of complement systems and in the maintenance of integrity in nerve tissues. Proc Natl Acad Sci U S A 106:22405–22410

    Article  PubMed  CAS  Google Scholar 

  43. Ohmi Y, Tajima O, Ohkawa Y, Yamauchi Y, Sugiura Y, Furukawa K (2011) Gangliosides are essential in the protection of inflammation and neurodegeneration via maintenance of lipid rafts: elucidation by a series of ganglioside-deficient mutant mice. J Neurochem 116:926–935

    Article  PubMed  CAS  Google Scholar 

  44. Kawai H, Allende ML, Wada R et al (2001) Mice expressing only monosialoganglioside GM3 exhibit lethal audiogenic seizures. J Biol Chem 276:6885–6888

    Article  PubMed  CAS  Google Scholar 

  45. Okada M, Itoh Mi M, Haraguchi M et al (2002) b-series Ganglioside deficiency exhibits no definite changes in the neurogenesis and the sensitivity to Fas-mediated apoptosis but impairs regeneration of the lesioned hypoglossal nerve. J Biol Chem 277:1633–1636

    Article  PubMed  CAS  Google Scholar 

  46. Dupree JL, Coetzee T, Suzuki K, Popko B (1998) Myelin abnormalities in mice deficient in galactocerebroside and sulfatide. J Neurocytol 27:649–659

    Article  PubMed  CAS  Google Scholar 

  47. Ezoe T, Vanier MT, Oya Y et al (2000) Biochemistry and neuropathology of mice doubly deficient in synthesis and degradation of galactosylceramide. J Neurosci Res 59:170–178

    Article  PubMed  CAS  Google Scholar 

  48. Furukawa K, Takamiya K, Okada M, Inoue M, Fukumoto S, Furukawa K (2001) Novel functions of complex carbohydrates elucidated by the mutant mice of glycosyltransferase genes. Biochim Biophys Acta 1525:1–12

    Article  PubMed  CAS  Google Scholar 

  49. Takamiya K, Yamamoto A, Furukawa K et al (1996) Mice with disrupted GM2/GD2 synthase gene lack complex gangliosides but exhibit only subtle defects in their nervous system. Proc Natl Acad Sci U S A 93:10662–10667

    Article  PubMed  CAS  Google Scholar 

  50. Yamashita T, Wu YP, Sandhoff R et al (2005) Interruption of ganglioside synthesis produces central nervous system degeneration and altered axon-glial interactions. Proc Natl Acad Sci U S A 102:2725–2730

    Article  PubMed  CAS  Google Scholar 

  51. Yoshikawa M, Go S, Takasaki K et al (2009) Mice lacking ganglioside GM3 synthase exhibit complete hearing loss due to selective degeneration of the organ of Corti. Proc Natl Acad Sci U S A 106:9483–9488

    Article  PubMed  CAS  Google Scholar 

  52. Yu RK, Tsai YT, Ariga T, Yanagisawa M (2011) Structures, biosynthesis, and functions of gangliosides-an overview. J Oleo Sci 60:537–544

    Article  PubMed  CAS  Google Scholar 

  53. McKay R (1997) Stem cells in the central nervous system. Science 276:66–71

    Article  PubMed  CAS  Google Scholar 

  54. Temple S, Alvarez-Buylla A (1999) Stem cells in the adult mammalian central nervous system. Curr Opin Neurobiol 9:135–141

    Article  PubMed  CAS  Google Scholar 

  55. Weiss S, Reynolds BA, Vescovi AL, Morshead C, Craig CG, van der Kooy D (1996) Is there a neural stem cell in the mammalian forebrain? Trends Neurosci 19:387–393

    Article  PubMed  CAS  Google Scholar 

  56. Yanagisawa M, Yu RK (2007) The expression and functions of glycoconjugates in neural stem cells. Glycobiology 17:57R–74R

    Article  PubMed  CAS  Google Scholar 

  57. Liour SS, Dinkins MB, Su CY, Yu RK (2005) Spatiotemporal expression of GM1 in murine medial pallial neural progenitor cells. J Comp Neurol 491:330–338

    Article  PubMed  CAS  Google Scholar 

  58. Liour SS, Kraemer SA, Dinkins MB, Su CY, Yanagisawa M, Yu RK (2006) Further characterization of embryonic stem cell-derived radial glial cells. Glia 53:43–56

    Article  PubMed  Google Scholar 

  59. Yanagisawa M, Taga T, Nakamura K, Ariga T, Yu RK (2005) Characterization of glycoconjugate antigens in mouse embryonic neural precursor cells. J Neurochem 95:1311–1320

    Article  PubMed  CAS  Google Scholar 

  60. Yang CR, Liour SS, Dasgupta S, Yu RK (2007) Inhibition of neuronal migration by JONES antibody is independent of 9-O-acetyl GD3 in GD3-synthase knockout mice. J Neurosci Res 85:1381–1390

    Article  PubMed  CAS  Google Scholar 

  61. Yu RK, Yanagisawa M (2007) Glycosignaling in neural stem cells: involvement of glycoconjugates in signal transduction modulating the neural stem cell fate. J Neurochem 103(Suppl 1):39–46

    Article  PubMed  CAS  Google Scholar 

  62. Doetsch F, Caille I, Lim DA, Garcia-Verdugo JM, Alvarez-Buylla A (1999) Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97:703–716

    Article  PubMed  CAS  Google Scholar 

  63. Seri B, Garcia-Verdugo JM, McEwen BS, Alvarez-Buylla A (2001) Astrocytes give rise to new neurons in the adult mammalian hippocampus. J Neurosci 21:7153–7160

    PubMed  CAS  Google Scholar 

  64. Yanagisawa M, Nakamura K, Taga T (2004) Roles of lipid rafts in integrin-dependent adhesion and gp130 signalling pathway in mouse embryonic neural precursor cells. Genes Cells 9:801–809

    Article  PubMed  CAS  Google Scholar 

  65. Suzuki Y, Yanagisawa M, Yagi H, Nakatani Y, Yu RK (2010) Involvement of beta1-integrin up-regulation in basic fibroblast growth factor- and epidermal growth factor-induced proliferation of mouse neuroepithelial cells. J Biol Chem 285:18443–18451

    Article  PubMed  CAS  Google Scholar 

  66. Yanagisawa M, Nakamura K, Taga T (2005) Glycosphingolipid synthesis inhibitor represses cytokine-induced activation of the Ras-MAPK pathway in embryonic neural precursor cells. J Biochem 138:285–291

    Article  PubMed  CAS  Google Scholar 

  67. Ohkawa Y, Miyazaki S, Hamamura K et al (2010) Ganglioside GD3 enhances adhesion signals and augments malignant properties of melanoma cells by recruiting integrins to glycolipid-enriched microdomains. J Biol Chem 285:27213–27223

    Article  PubMed  CAS  Google Scholar 

  68. Jennemann R, Sandhoff R, Wang S et al (2005) Cell-specific deletion of glucosylceramide synthase in brain leads to severe neural defects after birth. Proc Natl Acad Sci U S A 102:12459–12464

    Article  PubMed  CAS  Google Scholar 

  69. Jung JU, Ko K, Lee DH, Ko K, Chang KT, Choo YK (2009) The roles of glycosphingolipids in the proliferation and neural differentiation of mouse embryonic stem cells. Exp Mol Med 41:935–945

    Article  PubMed  CAS  Google Scholar 

  70. Shevchuk NA, Hathout Y, Epifano O et al (2007) Alteration of ganglioside synthesis by GM3 synthase knockout in murine embryonic fibroblasts. Biochim Biophys Acta 1771:1226–1234

    PubMed  CAS  Google Scholar 

  71. Niimi K, Nishioka C, Miyamoto T et al (2011) Impairment of neuropsychological behaviors in ganglioside GM3-knockout mice. Biochem Biophys Res Commun 406:524–528

    Article  PubMed  CAS  Google Scholar 

  72. Handa Y, Ozaki N, Honda T et al (2005) GD3 synthase gene knockout mice exhibit thermal hyperalgesia and mechanical allodynia but decreased response to formalin-induced prolonged noxious stimulation. Pain 117:271–279

    Article  PubMed  CAS  Google Scholar 

  73. Furukawa K, Aixinjueluo W, Kasama T et al (2008) Disruption of GM2/GD2 synthase gene resulted in overt expression of 9-O-acetyl GD3 irrespective of Tis21. J Neurochem 105:1057–1066

    Article  PubMed  CAS  Google Scholar 

  74. Sheikh KA, Sun J, Liu Y et al (1999) Mice lacking complex gangliosides develop Wallerian degeneration and myelination defects. Proc Natl Acad Sci U S A 96:7532–7537

    Article  PubMed  CAS  Google Scholar 

  75. Chiavegatto S, Sun J, Nelson RJ, Schnaar RL (2000) A functional role for complex gangliosides: motor deficits in GM2/GD2 synthase knockout mice. Exp Neurol 166:227–234

    Article  PubMed  CAS  Google Scholar 

  76. Sugiura Y, Furukawa K, Tajima O, Mii S, Honda T (2005) Sensory nerve-dominant nerve degeneration and remodeling in the mutant mice lacking complex gangliosides. Neuroscience 135:1167–1178

    Article  PubMed  CAS  Google Scholar 

  77. Tajima O, Egashira N, Ohmi Y et al (2009) Reduced motor and sensory functions and emotional response in GM3-only mice: emergence from early stage of life and exacerbation with aging. Behav Brain Res 198:74–82

    Article  PubMed  Google Scholar 

  78. Tajima O, Egashira N, Ohmi Y et al (2010) Dysfunction of muscarinic acetylcholine receptors as a substantial basis for progressive neurological deterioration in GM3-only mice. Behav Brain Res 206:101–108

    Article  PubMed  CAS  Google Scholar 

  79. Inoue M, Fujii Y, Furukawa K et al (2002) Refractory skin injury in complex knock-out mice expressing only the GM3 ganglioside. J Biol Chem 277:29881–29888

    Article  PubMed  CAS  Google Scholar 

  80. Yamashita T, Hashiramoto A, Haluzik M et al (2003) Enhanced insulin sensitivity in mice lacking ganglioside GM3. Proc Natl Acad Sci U S A 100:3445–3449

    Article  PubMed  CAS  Google Scholar 

  81. de la Monte SM, Wands JR (2005) Review of insulin and insulin-like growth factor expression, signaling, and malfunction in the central nervous system: relevance to Alzheimer’s disease. J Alzheimer’s Dis JAD 7:45–61

    Google Scholar 

  82. Farukhi F, Dakkouri C, Wang H, Wiztnitzer M, Traboulsi EI (2006) Etiology of vision loss in ganglioside GM3 synthase deficiency. Ophthalmic Genet 27:89–91

    Article  PubMed  CAS  Google Scholar 

  83. Yanagisawa K (2011) Pathological significance of ganglioside clusters in Alzheimer’s disease. J Neurochem 116:806–812

    Article  PubMed  CAS  Google Scholar 

  84. Ariga T, McDonald MP, Yu RK (2008) Role of ganglioside metabolism in the pathogenesis of Alzheimer’s disease–a review. J Lipid Res 49:1157–1175

    Article  PubMed  CAS  Google Scholar 

  85. Ariga T, Wakade C, Yu RK (2011) The pathological roles of ganglioside metabolism in Alzheimer’s disease: effects of gangliosides on neurogenesis. Int J Alzheimers Dis. doi:10.4061/2011/193618

    PubMed  Google Scholar 

  86. Oikawa N, Yamaguchi H, Ogino K et al (2009) Gangliosides determine the amyloid pathology of Alzheimer’s disease. NeuroReport 20:1043–1046

    PubMed  CAS  Google Scholar 

  87. Bernardo A, Harrison FE, McCord M et al (2009) Elimination of GD3 synthase improves memory and reduces amyloid-beta plaque load in transgenic mice. Neurobiol Aging 30:1777–1791

    Article  PubMed  CAS  Google Scholar 

  88. Ando S, Hirabayashi Y, Kon K, Inagaki F, Tate S, Whittaker VP (1992) A trisialoganglioside containing a sialyl alpha 2–6 N-acetylgalactosamine residue is a cholinergic-specific antigen, Chol-1 alpha. J Biochem 111:287–290

    PubMed  CAS  Google Scholar 

  89. Ariga T, Yanagisawa M, Wakade C et al (2010) Ganglioside metabolism in a transgenic mouse model of Alzheimer’s disease: expression of Chol-1alpha antigens in the brain. ASN Neuro 2:e00044

    Article  PubMed  CAS  Google Scholar 

  90. Wu G, Lu ZH, Kulkarni N, Amin R, Ledeen RW (2011) Mice lacking major brain gangliosides develop parkinsonism. Neurochem Res 36:1706–1714

    Article  PubMed  CAS  Google Scholar 

  91. Kaida K, Ariga T, Yu RK (2009) Antiganglioside antibodies and their pathophysiological effects on Guillain-Barré syndrome and related disorders–a review. Glycobiology 19:676–692

    Article  PubMed  CAS  Google Scholar 

  92. Yu RK, Usuki S, Ariga T (2006) Ganglioside molecular mimicry and its pathological roles in Guillain-Barré syndrome and related diseases. Infect Immun 74:6517–6527

    Article  PubMed  CAS  Google Scholar 

  93. Yu RK, Ariga T, Usuki S, Kaida K (2011) Pathological roles of ganglioside mimicry in Guillain-Barré syndrome and related neuropathies. Adv Exp Med Biol 705:349–365

    Article  PubMed  Google Scholar 

  94. Willison HJ, Yuki N (2002) Peripheral neuropathies and anti-glycolipid antibodies. Brain 125:2591–2625

    Article  PubMed  Google Scholar 

  95. Ariga T, Yu RK (2005) Antiglycolipid antibodies in Guillain-Barre syndrome and related diseases: review of clinical features and antibody specificities. J Neurosci Res 80:1–17

    Article  PubMed  CAS  Google Scholar 

  96. Bullens RW, O’Hanlon GM, Wagner E et al (2002) Complex gangliosides at the neuromuscular junction are membrane receptors for autoantibodies and botulinum neurotoxin but redundant for normal synaptic function. J Neurosci 22:6876–6884

    PubMed  CAS  Google Scholar 

  97. Zitman FM, Todorov B, Jacobs BC et al (2008) Neuromuscular synaptic function in mice lacking major subsets of gangliosides. Neuroscience 156:885–897

    Article  PubMed  CAS  Google Scholar 

  98. Susuki K, Baba H, Tohyama K et al (2007) Gangliosides contribute to stability of paranodal junctions and ion channel clusters in myelinated nerve fibers. Glia 55:746–757

    Article  PubMed  Google Scholar 

  99. Desplats PA, Denny CA, Kass KE et al (2007) Glycolipid and ganglioside metabolism imbalances in Huntington’s disease. Neurobiol Dis 27:265–277

    Article  PubMed  CAS  Google Scholar 

  100. Denny CA, Desplats PA, Thomas EA, Seyfried TN (2010) Cerebellar lipid differences between R6/1 transgenic mice and humans with Huntington’s disease. J Neurochem 115:748–758

    Article  PubMed  CAS  Google Scholar 

  101. Higatsberger MR, Sperk G, Bernheimer H, Shannak KS, Hornykiewicz O (1981) Striatal ganglioside levels in the rat following kainic acid lesions: comparison with Huntington’s disease. Exp Brain Res 44:93–96

    Article  PubMed  CAS  Google Scholar 

  102. Svennerholm L (1963) Chromatographic separation of human brain gangliosides. J Neurochem 10:613–623

    Article  PubMed  CAS  Google Scholar 

  103. IUPAC-IUBMB Joint Commission on Biochemical Nomenclature (1997) Nomenclature of glycolipids. Pure Appl Chem 69:2475–2487

    Article  Google Scholar 

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Acknowledgments

This study was supported by USPHS grants (NS11853-36 and NS26994-21), a Veteran’s Administration Merit Review Award (1IO1BX001388-01), and a grant from the Children’s Medical Research Foundation, Chicago, IL, to RKY. RKY also grateful acknowledges the contributions from many of his past and present collaborators for the work performed in his laboratory. It is a great pleasure to contribute to this special issue of “Neurochemical Research” honoring Dr. Robert W. Ledeen whose pioneering contributions to the field of ganglioside research have greatly enriched the field. RKY is also deeply indebted to him for his initiation and guidance into the ganglioside field during the early phase of his career development at the Albert Einstein College of Medicine, Bronx, NY.

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  1. Institute of Molecular Medicine and Genetics and Institute of Neuroscience, Medical College of Georgia, Georgia Health Sciences University, 1120 15th Street, Augusta, GA, 30912, USA

    Robert K. Yu, Yi-Tzang Tsai & Toshio Ariga

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  1. Robert K. Yu
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  2. Yi-Tzang Tsai
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  3. Toshio Ariga
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Correspondence to Robert K. Yu.

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Special issue: In honor of Bob Leeden.

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Yu, R.K., Tsai, YT. & Ariga, T. Functional Roles of Gangliosides in Neurodevelopment: An Overview of Recent Advances. Neurochem Res 37, 1230–1244 (2012). https://doi.org/10.1007/s11064-012-0744-y

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