The Pathogenic Role of Ganglioside Metabolism in Alzheimer’s Disease-Cholinergic Neuron-Specific Gangliosides and Neurogenesis

Molecular Neurobiology

Volumn 54, Issue 1, 2017, Pages 623-638

  Ariga, Toshio ^a,b  

^a MEDICAL COLLEGE OF GEORGIA   (United States)

^b NIHON UNIVERSITY   (Japan)

Author keywords

Alzheimer s disease; Chol 1 ; Gangliosides; Lipid rafts; Treatment

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID PRECURSOR PROTEIN; GANGLIOSIDE; GANGLIOSIDE ANTIBODY; GANGLIOSIDE GD 1A; GANGLIOSIDE GD 1B; GANGLIOSIDE GD3; GANGLIOSIDE GM1; GANGLIOSIDE GM2; GANGLIOSIDE GM3; GANGLIOSIDE GM4; GANGLIOSIDE GQ 1B ALPHA; GANGLIOSIDE GT 1A ALPHA; GANGLIOSIDE GT 1B; GANGLIOSIDE GT3; IMMUNOGLOBULIN M ANTIBODY; LIGA 20; SIALIC ACID BINDING IMMUNOGLOBULIN LIKE LECTIN; SIALIDASE; SIGLEC 11; SPHINGOSINE DERIVATIVE; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; AMYLOID PLAQUE; ANTIBODY TITER; BLOOD BRAIN BARRIER; CEREBROVASCULAR ACCIDENT; CHOLINERGIC NERVE CELL; COGNITIVE DEFECT; CONFORMATIONAL TRANSITION; DIAGNOSTIC VALUE; DISEASE SEVERITY; GANGLIOSIDE METABOLISM; HUMAN; LIPID METABOLISM; LIPID RAFT; MULTIINFARCT DEMENTIA; NERVE DEGENERATION; NERVOUS SYSTEM DEVELOPMENT; NEURAL STEM CELL; NEUROPROTECTION; NONHUMAN; PARKINSONISM; PATHOGENESIS; PROGNOSIS; PROTEIN AGGREGATION; PROTEIN LIPID INTERACTION; PROTEIN MISFOLDING; REVIEW; SPINAL CORD INJURY; ANIMAL; BRAIN; MEMBRANE MICRODOMAIN; METABOLISM; PATHOLOGY; PHYSIOLOGY;

ALZHEIMER DISEASE; ANIMALS; BRAIN; CHOLINERGIC NEURONS; GANGLIOSIDES; HUMANS; MEMBRANE MICRODOMAINS; NEUROGENESIS;

EID: 84953404703     PISSN: 08937648     EISSN: 15591182     Source Type: Journal    
DOI: 10.1007/s12035-015-9641-0     Document Type: Review

References (155)

1. Svennerholm L (1963) Chromatographic separation of human brain gangliosides. J Neurochem 10:613–623
2. (1977) The nomenclature of lipids. Recommendations (1976) IUPAC-IUB Commission on Biochemical Nomenclature. Lipids 12: 455–468
3. Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM (2007) Forecasting the global burden of Alzheimer’s disease. Alzheimers Dement 3:186–191
4. Nussbaum RL, Ellis CE (2003) Alzheimer’s disease and Parkinson’s disease. N Engl J Med 348:1356–1364
5. 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
6. 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 2011:193618
7. Lee SJ, Liyanage U, Bickel PE, Xia W, Lansbury PT Jr et al (1998) A detergent-insoluble membrane compartment contains A beta in vivo. Nat Med 4:730–734
8. Kotani M, Ozawa H, Kawashima I, Ando S, Tai T (1992) Generation of one set of monoclonal antibodies specific for a-pathway ganglio-series gangliosides. Biochim Biophys Acta 1117:97–103
9. Zitman FM, Todorov B, Furukawa K, Willison HJ, Plomp JJ (2010) Total ganglioside ablation at mouse motor nerve terminals alters neurotransmitter release level. Synapse 64:335–338
10. Yu RK (1994) Development regulation of ganglioside metabolism. Prog Brain Res 101:31–44
11. Yates AJ (1986) Gangliosides in the nervous system during development and regeneration. Neurochem Pathol 5:309–329
12. Hakomori Si SI (2002) The glycosynapse. Proc Natl Acad Sci U S A 99:225–232
13. Yu RK, Nakatani Y, Yanagisawa M (2009) The role of glycosphingolipid metabolism in the developing brain. J Lipid Res 50(Suppl):S440–S445
14. Hakomori S (2000) Traveling for the glycosphingolipid path. Glycoconj J 17:627–647
15. Simons K, Toomre D (2000) Lipid rafts and signal transduction. Nat Rev Mol Cell Biol 1:31–39
16. Martin V, Fabelo N, Santpere G, Puig B, Marin R et al (2010) Lipid alterations in lipid rafts from Alzheimer’s disease human brain cortex. J Alzheimers Dis 19:489–502
17. Malchiodi-Albedi F, Paradisi S, Matteucci A, Frank C, Diociaiuti M (2011) Amyloid oligomer neurotoxicity, calcium dysregulation, and lipid rafts. Int J Alzheimers Dis 2011:906964
18. Ariga T, Kobayashi K, Hasegawa A, Kiso M, Ishida H et al (2001) Characterization of high-affinity binding between gangliosides and amyloid beta-protein. Arch Biochem Biophys 388:225–230
19. Choo-Smith LP, Garzon-Rodriguez W, Glabe CG, Surewicz WK (1997) Acceleration of amyloid fibril formation by specific binding of Abeta-(1–40) peptide to ganglioside-containing membrane vesicles. J Biol Chem 272:22987–22990
20. Yanagisawa K (2011) Pathological significance of ganglioside clusters in Alzheimer’s disease. J Neurochem 116:806–812
21. Matsuzaki K (2011) Formation of toxic amyloid fibrils by amyloid beta-protein on ganglioside clusters. Int J Alzheimers Dis 2011:956104
22. Schneider JS (2014) Gangliosides and glycolipids in neurodegenerative disorders. Adv Neurobiol 9:449–461
23. Ariga T (2014) Pathogenic role of ganglioside metabolism in neurodegenerative diseases. J Neurosci Res 92:1227–1242
24. Schengrund CL (2010) Lipid rafts: keys to neurodegeneration. Brain Res Bull 82:7–17
25. Yu RK, Tsai YT, Ariga T (2012) Functional roles of gangliosides in neurodevelopment: an overview of recent advances. Neurochem Res 37:1230–1244
26. Irie F, Hidari KI, Tai T, Li YT, Seyama Y et al (1994) Biosynthetic pathway for a new series of gangliosides, GT1a alpha and GQ1b alpha. FEBS Lett 351:291–294
27. Grimm MO, Tschape JA, Grimm HS, Zinser EG, Hartmann T (2006) Altered membrane fluidity and lipid raft composition in presenilin-deficient cells. Acta Neurol Scand Suppl 185:27–32
28. Yadav RS, Tiwari NK (2014) Lipid integration in neurodegeneration: an overview of Alzheimer’s disease. Mol Neurobiol 50:168–176
29. Piccinini M, Scandroglio F, Prioni S, Buccinna B, Loberto N et al (2010) Deregulated sphingolipid metabolism and membrane organization in neurodegenerative disorders. Mol Neurobiol 41:314–340
30. Svennerholm L (1994) Ganglioside loss is a primary event in Alzheimer disease type I. Prog Brain Res 101:391–404
31. Crino PB, Ullman MD, Vogt BA, Bird ED, Volicer L (1989) Brain gangliosides in dementia of the Alzheimer type. Arch Neurol 46:398–401
32. Kracun I, Kalanj S, Cosovic C, Talan-Hranilovic J (1990) Brain gangliosides in Alzheimer’s disease. J Hirnforsch 31:789–793
33. Kracun I, Rosner H, Drnovsek V, Heffer-Lauc M, Cosovic C et al (1991) Human brain gangliosides in development, aging and disease. Int J Dev Biol 35:289–295
34. Kracun I, Kalanj S, Talan-Hranilovic J, Cosovic C (1992) Cortical distribution of gangliosides in Alzheimer’s disease. Neurochem Int 20:433–438
35. Svennerholm L, Gottfries CG (1994) Membrane lipids, selectively diminished in Alzheimer brains, suggest synapse loss as a primary event in early-onset form (type I) and demyelination in late-onset form (type II). J Neurochem 62:1039–1047
36. Kalanj S, Kracun I, Rosner H, Cosovic C (1991) Regional distribution of brain gangliosides in Alzheimer’s disease. Neurol Croat 40:269–281
37. Molander-Melin M, Blennow K, Bogdanovic N, Dellheden B, Mansson JE et al (2005) Structural membrane alterations in Alzheimer brains found to be associated with regional disease development; increased density of gangliosides GM1 and GM2 and loss of cholesterol in detergent-resistant membrane domains. J Neurochem 92:171–182
38. Brooksbank BW, McGovern J (1989) Gangliosides in the brain in adult Down’s syndrome and Alzheimer’s disease. Mol Chem Neuropathol 11:143–156
39. Valdes-Gonzalez T, Goto-Inoue N, Hirano W, Ishiyama H, Hayasaka T et al (2011) New approach for glyco- and lipidomics–molecular scanning of human brain gangliosides by TLC-Blot and MALDI-QIT-TOF MS. J Neurochem 116:678–683
40. Taki T (2012) An approach to glycobiology from glycolipidomics: ganglioside molecular scanning in the brains of patients with Alzheimer’s disease by TLC-blot/matrix assisted laser desorption/ionization-time of flight MS. Biol Pharm Bull 35:1642–1647
41. Kracun I, Rosner H, Drnovsek V, Vukelic Z, Cosovic C et al (1992) Gangliosides in the human brain development and aging. Neurochem Int 20:421–431
42. Blennow K, Davidsson P, Wallin A, Fredman P, Gottfries CG et al (1992) Differences in cerebrospinal fluid gangliosides between “probable Alzheimer’s disease” and normal aging. Aging (Milano) 4:301–306
43. Chan RB, Oliveira TG, Cortes EP, Honig LS, Duff KE et al (2012) Comparative lipidomic analysis of mouse and human brain with Alzheimer disease. J Biol Chem 287:2678–2688
44. Scorrano L, Petronilli V, Di Lisa F, Bernardi P (1999) Commitment to apoptosis by GD3 ganglioside depends on opening of the mitochondrial permeability transition pore. J Biol Chem 274:22581–22585
45. Yu RK, Iqbal K (1979) Sialosylgalactosyl ceramide as a specific marker for human myelin and oligodendroglial perikarya: gangliosides of human myelin, oligodendroglia and neurons. J Neurochem 32:293–300
46. Pitto M, Raimondo F, Zoia C, Brighina L, Ferrarese C et al (2005) Enhanced GM1 ganglioside catabolism in cultured fibroblasts from Alzheimer patients. Neurobiol Aging 26:833–838
47. Pernber Z, Blennow K, Bogdanovic N, Mansson JE, Blomqvist M (2012) Altered distribution of the gangliosides GM1 and GM2 in Alzheimer’s disease. Dement Geriatr Cogn Disord 33:174–188
48. Oikawa N, Yamaguchi H, Ogino K, Taki T, Yuyama K et al (2009) Gangliosides determine the amyloid pathology of Alzheimer’s disease. Neuroreport 20:1043–1046
49. Barrier L, Ingrand S, Damjanac M, Rioux Bilan A, Hugon J et al (2007) Genotype-related changes of ganglioside composition in brain regions of transgenic mouse models of Alzheimer’s disease. Neurobiol Aging 28:1863–1872
50. Bernardo A, Harrison FE, McCord M, Zhao J, Bruchey A et al (2009) Elimination of GD3 synthase improves memory and reduces amyloid-beta plaque load in transgenic mice. Neurobiol Aging 30:1777–1791
51. Sawamura N, Morishima-Kawashima M, Waki H, Kobayashi K, Kuramochi T et al (2000) Mutant presenilin 2 transgenic mice. A large increase in the levels of Abeta 42 is presumably associated with the low density membrane domain that contains decreased levels of glycerophospholipids and sphingomyelin. J Biol Chem 275:27901–27908
52. Ariga T, Yanagisawa M, Wakade C, Ando S, Buccafusco JJ et al (2010) Ganglioside metabolism in a transgenic mouse model of Alzheimer’s disease: expression of Chol-1alpha antigens in the brain. ASN Neuro 2:233–241
53. Keilani S, Lun Y, Stevens AC, Williams HN, Sjoberg ER et al (2012) Lysosomal dysfunction in a mouse model of Sandhoff disease leads to accumulation of ganglioside-bound amyloid-beta peptide. J Neurosci 32:5223–5236
54. Ariga T, Itokazu Y, McDonald MP, Hirabayashi Y, Ando S et al (2013) Brain gangliosides of a transgenic mouse model of Alzheimer’s disease with deficiency in GD3-synthase: expression of elevated levels of a cholinergic-specific ganglioside, GT1aalpha. ASN Neuro 5:141–148
55. Fukami Y, Ariga T, Yamada M, Yuki N (2015) Higher expression of cholinergic neuron-specific gangliosides in Alzheimer’s disease. Current Alzheimer Research: submitted
56. Richardson PJ, Walker JH, Jones RT, Whittaker VP (1982) Identification of a cholinergic-specific antigen Chol-1 as a ganglioside. J Neurochem 38:1605–1614
57. Derrington EA, Borroni E (1990) The developmental expression of the cholinergic-specific antigen Chol-1 in the central and peripheral nervous system of the rat. Brain Res Dev Brain Res 52:131–140
58. Whittaker VP, Derrington EA, Borroni E (1992) Chol-1 is a cholinergic marker in the human central nervous system. Neuroreport 3:341–344
59. Ando S, Tanaka Y, Kobayashi S, Fukui F, Iwamoto M et al (2004) Synaptic function of cholinergic-specific Chol-1alpha ganglioside. Neurochem Res 29:857–867
60. Ando S, Tanaka Y, Waki H, Kon K, Iwamoto M et al (1998) Gangliosides and sialylcholesterol as modulators of synaptic functions. Ann N Y Acad Sci 845:232–239
61. 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
62. Greenberg DA, Jin K (2006) Neurodegeneration and neurogenesis: focus on Alzheimer’s disease. Curr Alzheimer Res 3:25–28
63. Jin K, Galvan V, Xie L, Mao XO, Gorostiza OF et al (2004) Enhanced neurogenesis in Alzheimer’s disease transgenic (PDGF-APPSw, Ind) mice. Proc Natl Acad Sci U S A 101:13363–13367
64. Jin K, Peel AL, Mao XO, Xie L, Cottrell BA et al (2004) Increased hippocampal neurogenesis in Alzheimer’s disease. Proc Natl Acad Sci U S A 101:343–347
65. Lopez-Toledano MA, Ali Faghihi M, Patel NS, Wahlestedt C (2010) Adult neurogenesis: a potential tool for early diagnosis in Alzheimer’s disease? J Alzheimers Dis 20:395–408
66. Liu L, Zhang K, Tan L, Chen YH, Cao YP (2015) Alterations in cholesterol and ganglioside GM1 content of lipid rafts in platelets from patients with Alzheimer disease. Alzheimer Dis Assoc Disord 29:63–69
67. Yuki N, Ariga T (1997) Antibodies to fucogangliosides in neurological diseases. J Neurol Sci 150:81–84
68. Lehmann HC, Lopez PH, Zhang G, Ngyuen T, Zhang J et al (2007) Passive immunization with anti-ganglioside antibodies directly inhibits axon regeneration in an animal model. J Neurosci 27:27–34
69. Chapman J, Sela BA, Wertman E, Michaelson DM (1988) Antibodies to ganglioside GM1 in patients with Alzheimer’s disease. Neurosci Lett 86:235–240
70. Hatzifilippou E, Koutsouraki E, Banaki T, Traka M, Costa VG et al (2008) Antibodies against GM1 in demented patients. Am J Alzheimers Dis Other Demen 23:274–279
71. Koutsouraki E, Hatzifilippou E, Michmizos D, Banaki T, Costa V et al (2014) The probable auto-antigenic role of lipids (anti-ganglioside antibodies) in the pathogenesis of Alzheimer’s disease. J Alzheimers Dis 42(Suppl 3):S163–S166
72. Hatzifilippou E, Koutsouraki E, Costa VG, Baloyannis SJ (2014) Antibodies against gangliosides in patients with dementia. Am J Alzheimers Dis Other Demen 29:660–666
73. Ariga T, Kubota M, Nakane M, Oguro K, Yu RK et al (2013) Anti-Chol-1 antigen, GQ1balpha, antibodies are associated with Alzheimer’s disease. PLoS One 8:e63326
74. Michaelson DM, Chapman J, Bachar O, Korczyn AD, Wertman E (1989) Serum antibodies to cholinergic neurons in Alzheimer’s disease. Prog Clin Biol Res 317:689–694
75. Chapman J, Bachar O, Korczyn AD, Wertman E, Michaelson DM (1988) Antibodies to cholinergic neurons in Alzheimer’s disease. J Neurochem 51:479–485
76. Miura Y, Miyaji K, Chai YL, Chen CL, Lai MK et al (2014) Autoantibodies to GM1 and GQ1balpha are not Biological Markers of Alzheimer’s Disease. J Alzheimers Dis 42:1165–1169
77. Huflejt ME, Vuskovic M, Vasiliu D, Xu H, Obukhova P et al (2009) Anti-carbohydrate antibodies of normal sera: findings, surprises and challenges. Mol Immunol 46:3037–3049
78. Okada N, Yasuda T, Tsumita T, Okada H (1983) Activation of the alternative complement pathway by natural antibody to glycolipids in guinea-pig serum. Immunology 50:75–84
79. Mitzutamari RK, Kremer LJ, Basile EA, Nores GA (1998) Anti-GM1 ganglioside IgM-antibodies present in human plasma: affinity and biological activity changes in a patient with neuropathy. J Neurosci Res 51:237–242
80. Clifford PM, Zarrabi S, Siu G, Kinsler KJ, Kosciuk MC et al (2007) Abeta peptides can enter the brain through a defective blood–brain barrier and bind selectively to neurons. Brain Res 1142:223–236
81. Grammas P (2011) Neurovascular dysfunction, inflammation and endothelial activation: implications for the pathogenesis of Alzheimer’s disease. J Neuroinflammation 8:26
82. Sadatipour BT, Greer JM, Pender MP (1998) Increased circulating antiganglioside antibodies in primary and secondary progressive multiple sclerosis. Ann Neurol 44:980–983
83. Ravindranath MH, Muthugounder S, Saravanan TS, Presser N, Morton DL (2005) Human antiganglioside autoantibodies: validation of ELISA. Ann N Y Acad Sci 1050:229–242
84. Kanda T, Iwasaki T, Yamawaki M, Tai T, Mizusawa H (2000) Anti-GM1 antibody facilitates leakage in an in vitro blood-nerve barrier model. Neurology 55:585–587
85. Winer JB (2001) Guillain Barre syndrome. Mol Pathol 54:381–385
86. Kuwabara S, Ogawara K, Mizobuchi K, Koga M, Mori M et al (2000) Isolated absence of F waves and proximal axonal dysfunction in Guillain-Barre syndrome with antiganglioside antibodies. J Neurol Neurosurg Psychiatry 68:191–195
87. McLaurin J, Chakrabartty A (1996) Membrane disruption by Alzheimer beta-amyloid peptides mediated through specific binding to either phospholipids or gangliosides. Implications for neurotoxicity. J Biol Chem 271:26482–26489
88. Matsuzaki K, Horikiri C (1999) Interactions of amyloid beta-peptide (1–40) with ganglioside-containing membranes. Biochemistry 38:4137–4142
89. Yanagisawa K, Odaka A, Suzuki N, Ihara Y (1995) GM1 ganglioside-bound amyloid beta-protein (A beta): a possible form of preamyloid in Alzheimer’s disease. Nat Med 1:1062–1066
90. Yanagisawa M, Ariga T, Yu RK (2006) Fucosyl-GM1 expression and amyloid-beta protein accumulation in PC12 cells. J Neurosci Res 84:1343–1349
91. Yamamoto N, Matsuzaki K, Yanagisawa K (2005) Cross-seeding of wild-type and hereditary variant-type amyloid beta-proteins in the presence of gangliosides. J Neurochem 95:1167–1176
92. Kimura N, Yanagisawa K (2007) Endosomal accumulation of GM1 ganglioside-bound amyloid beta-protein in neurons of aged monkey brains. Neuroreport 18:1669–1673
93. Cataldo AM, Mathews PM, Boiteau AB, Hassinger LC, Peterhoff CM et al (2008) Down syndrome fibroblast model of Alzheimer-related endosome pathology: accelerated endocytosis promotes late endocytic defects. Am J Pathol 173:370–384
94. Ginsberg SD, Alldred MJ, Counts SE, Cataldo AM, Neve RL et al (2010) Microarray analysis of hippocampal CA1 neurons implicates early endosomal dysfunction during Alzheimer’s disease progression. Biol Psychiatry 68:885–893
95. Zha Q, Ruan Y, Hartmann T, Beyreuther K, Zhang D (2004) GM1 ganglioside regulates the proteolysis of amyloid precursor protein. Mol Psychiatry 9:946–952
96. Tamboli IY, Prager K, Barth E, Heneka M, Sandhoff K et al (2005) Inhibition of glycosphingolipid biosynthesis reduces secretion of the beta-amyloid precursor protein and amyloid beta-peptide. J Biol Chem 280:28110–28117
97. Muniz M, Morsomme P, Riezman H (2001) Protein sorting upon exit from the endoplasmic reticulum. Cell 104:313–320
98. Matsuzaki K, Kato K, Yanagisawa K (2010) Abeta polymerization through interaction with membrane gangliosides. Biochim Biophys Acta 1801:868–877
99. Funk KE, Kuret J (2012) Lysosomal fusion dysfunction as a unifying hypothesis for Alzheimer’s disease pathology. Int J Alzheimers Dis 2012:752894
100. Hooper NM (2006) Foreword: lipid rafts/biophysics, cell signalling, trafficking and processing. Mol Membr Biol 23:1–3
101. Simons K, Ehehalt R (2002) Cholesterol, lipid rafts, and disease. J Clin Invest 110:597–603
102. Scheibel T, Buchner J (2006) Protein aggregation as a cause for disease. Handb Exp Pharmacol. 199–219
103. Dohm CP, Kermer P, Bahr M (2008) Aggregopathy in neurodegenerative diseases: mechanisms and therapeutic implication. Neurodegener Dis 5:321–338
104. Shastry BS (2003) Neurodegenerative disorders of protein aggregation. Neurochem Int 43:1–7
105. Brown DA, London E (1998) Functions of lipid rafts in biological membranes. Annu Rev Cell Dev Biol 14:111–136
106. Williamson R, Sutherland C (2011) Neuronal membranes are key to the pathogenesis of Alzheimer’s disease: the role of both raft and non-raft membrane domains. Curr Alzheimer Res 8:213–221
107. Vetrivel KS, Cheng H, Lin W, Sakurai T, Li T et al (2004) Association of gamma-secretase with lipid rafts in post-Golgi and endosome membranes. J Biol Chem 279:44945–44954
108. Greenfield JP, Tsai J, Gouras GK, Hai B, Thinakaran G et al (1999) Endoplasmic reticulum and trans-Golgi network generate distinct populations of Alzheimer beta-amyloid peptides. Proc Natl Acad Sci U S A 96:742–747
109. Maccioni HJ, Daniotti JL, Martina JA (1999) Organization of ganglioside synthesis in the Golgi apparatus. Biochim Biophys Acta 1437:101–118
110. Wakabayashi M, Matsuzaki K (2009) Ganglioside-induced amyloid formation by human islet amyloid polypeptide in lipid rafts. FEBS Lett 583:2854–2858
111. Kim SI, Yi JS, Ko YG (2006) Amyloid beta oligomerization is induced by brain lipid rafts. J Cell Biochem 99:878–889
112. Mizuno T, Nakata M, Naiki H, Michikawa M, Wang R et al (1999) Cholesterol-dependent generation of a seeding amyloid beta-protein in cell culture. J Biol Chem 274:15110–15114
113. Rushworth JV, Hooper NM (2010) Lipid Rafts: Linking Alzheimer’s Amyloid-beta Production, Aggregation, and Toxicity at Neuronal Membranes. Int J Alzheimers Dis 2011:603052
114. Walkley SU, Zervas M, Wiseman S (2000) Gangliosides as modulators of dendritogenesis in normal and storage disease-affected pyramidal neurons. Cereb Cortex 10:1028–1037
115. Yamamoto N, Tanida M, Kasahara R, Sobue K, Suzuki K (2014) Leptin inhibits amyloid beta-protein fibrillogenesis by decreasing GM1 gangliosides on the neuronal cell surface through PI3K/Akt/mTOR pathway. J Neurochem 131:323–332
116. Magini A, Polchi A, Tozzi A, Tancini B, Tantucci M et al (2015) Abnormal cortical lysosomal beta-hexosaminidase and beta-galactosidase activity at post-synaptic sites during Alzheimer’s disease progression. Int J Biochem Cell Biol 58:62–70
117. Ledeen RW (1984) Biology of gangliosides: neuritogenic and neuronotrophic properties. J Neurosci Res 12:147–159
118. Gorio A (1986) Ganglioside enhancement of neuronal differentiation, plasticity, and repair. CRC Crit Rev Clin Neurobiol 2:241–296
119. Tsuji S, Arita M, Nagai Y (1983) GQ1b, a bioactive ganglioside that exhibits novel nerve growth factor (NGF)-like activities in the two neuroblastoma cell lines. J Biochem 94:303–306
120. Posse de Chaves E, Sipione S (2010) Sphingolipids and gangliosides of the nervous system in membrane function and dysfunction. FEBS Lett 584:1748–1759
121. Geisler FH, Dorsey FC, Coleman WP (1991) Recovery of motor function after spinal-cord injury—a randomized, placebo-controlled trial with GM-1 ganglioside. N Engl J Med 324:1829–1838
122. Argentino C, Sacchetti ML, Toni D, Savoini G, D’Arcangelo E et al (1989) GM1 ganglioside therapy in acute ischemic stroke. Italian Acute Stroke Study—Hemodilution + Drug. Stroke 20:1143–1149
123. Ala T, Romero S, Knight F, Feldt K, Frey WH 2nd (1990) GM-1 treatment of Alzheimer’s disease. A pilot study of safety and efficacy. Arch Neurol 47:1126–1130
124. Flicker C, Ferris SH, Kalkstein D, Serby M (1994) A double-blind, placebo-controlled crossover study of ganglioside GM1 treatment for Alzheimer’s disease. Am J Psychiatry 151:126–129
125. Svennerholm L (1994) Gangliosides—a new therapeutic agent against stroke and Alzheimer’s disease. Life Sci 55:2125–2134
126. Augustinsson LE, Blennow K, Blomstrand C, Brane G, Ekman R et al (1997) Intracerebroventricular administration of GM1 ganglioside to presenile Alzheimer patients. Dement Geriatr Cogn Disord 8:26–33
127. Svennerholm L, Brane G, Karlsson I, Lekman A, Ramstrom I et al (2002) Alzheimer disease—effect of continuous intracerebroventricular treatment with GM1 ganglioside and a systematic activation programme. Dement Geriatr Cogn Disord 14:128–136
128. Matsuoka Y, Saito M, LaFrancois J, Gaynor K, Olm V et al (2003) Novel therapeutic approach for the treatment of Alzheimer’s disease by peripheral administration of agents with an affinity to beta-amyloid. J Neurosci 23:29–33
129. Yang R, Wang Q, Min L, Sui R, Li J et al (2013) Monosialoanglioside improves memory deficits and relieves oxidative stress in the hippocampus of rat model of Alzheimer’s disease. Neurol Sci 34:1447–1451
130. Saulino MF, Schengrund CL (1994) Differential accumulation of gangliosides by the brains of MPTP-lesioned mice. J Neurosci Res 37:384–391
131. Polo A, Kirschner G, Guidotti A, Costa E (1994) Brain content of glycosphingolipids after oral administration of monosialogangliosides GM1 and LIGA20 to rats. Mol Chem Neuropathol 21:41–53
132. Bachis A, Mocchetti I (2006) Semisynthetic sphingoglycolipid LIGA20 is neuroprotective against human immunodeficiency virus-gp120-mediated apoptosis. J Neurosci Res 83:890–896
133. Wu G, Lu ZH, Kulkarni N, Amin R, Ledeen RW (2011) Mice lacking major brain gangliosides develop parkinsonism. Neurochem Res 36:1706–1714
134. Schneider JS, DiStefano L (1993) LIGA 20 increases striatal dopamine levels in aged MPTP-treated mice refractory to GM1 ganglioside treatment. Neuroreport 5:103–104
135. Hayashi H, Kimura N, Yamaguchi H, Hasegawa K, Yokoseki T et al (2004) A seed for Alzheimer amyloid in the brain. J Neurosci 24:4894–4902
136. Yamamoto N, Yokoseki T, Shibata M, Yamaguchi H, Yanagisawa K (2005) Suppression of Abeta deposition in brain by peripheral administration of Fab fragments of anti-seed antibody. Biochem Biophys Res Commun 335:45–47
137. Cho SH, Sun B, Zhou Y, Kauppinen TM, Halabisky B et al (2011) CX3CR1 protein signaling modulates microglial activation and protects against plaque-independent cognitive deficits in a mouse model of Alzheimer disease. J Biol Chem 286:32713–32722
138. Salminen A, Kaarniranta K (2009) Siglec receptors and hiding plaques in Alzheimer’s disease. J Mol Med (Berl) 87:697–701
139. Wang Y, Neumann H (2010) Alleviation of neurotoxicity by microglial human Siglec-11. J Neurosci 30:3482–3488
140. Angata T, Kerr SC, Greaves DR, Varki NM, Crocker PR et al (2002) Cloning and characterization of human Siglec-11. A recently evolved signaling molecule that can interact with SHP-1 and SHP-2 and is expressed by tissue macrophages, including brain microglia. J Biol Chem 277:24466–24474
141. Linnartz B, Wang Y, Neumann H (2010) Microglial immunoreceptor tyrosine-based activation and inhibition motif signaling in neuroinflammation. Int J Alzheimers Dis. 2010
142. Dhanushkodi A, McDonald MP (2011) Intracranial V. cholerae sialidase protects against excitotoxic neurodegeneration. PLoS One 6:e29285
143. Furukawa K, Ohmi Y, Ohkawa Y, Tokuda N, Kondo Y et al (2011) Regulatory mechanisms of nervous systems with glycosphingolipids. Neurochem Res 36:1578–1586
144. Haughey NJ, Nath A, Chan SL, Borchard AC, Rao MS et al (2002) Disruption of neurogenesis by amyloid beta-peptide, and perturbed neural progenitor cell homeostasis, in models of Alzheimer’s disease. J Neurochem 83:1509–1524
145. Wu L, Sluiter AA, Guo HF, Balesar RA, Swaab DF et al (2008) Neural stem cells improve neuronal survival in cultured postmortem brain tissue from aged and Alzheimer patients. J Cell Mol Med 12:1611–1621
146. Lu P, Jones LL, Snyder EY, Tuszynski MH (2003) Neural stem cells constitutively secrete neurotrophic factors and promote extensive host axonal growth after spinal cord injury. Exp Neurol 181:115–129
147. Dunbar GL, Sandstrom MI, Rossignol J, Lescaudron L (2006) Neurotrophic enhancers as therapy for behavioral deficits in rodent models of Huntington’s disease: use of gangliosides, substituted pyrimidines, and mesenchymal stem cells. Behav Cogn Neurosci Rev 5:63–79
148. Yanagisawa M (2011) Stem cell glycolipids. Neurochem Res 36:1623–1635
149. Blurton-Jones M, Kitazawa M, Martinez-Coria H, Castello NA, Muller FJ et al (2009) Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer disease. Proc Natl Acad Sci U S A 106:13594–13599
150. Gu G, Zhang W, Li M, Ni J, Wang P (2015) Transplantation of NSC-derived cholinergic neuron-like cells improves cognitive function in APP/PS1 transgenic mice. Neuroscience 291C:81–92
151. Zhang Q, Huang Y, Li X, Cui X, Zuo P et al (2005) GM1 ganglioside prevented the decline of hippocampal neurogenesis associated with D-galactose. Neuroreport 16:1297–1301
152. Wang J, Cheng A, Wakade C, Yu RK (2014) Ganglioside GD3 is required for neurogenesis and long-term maintenance of neural stem cells in the postnatal mouse brain. J Neurosci 34:13790–13800
153. Hicks DA, Nalivaeva NN, Turner AJ (2012) Lipid rafts and Alzheimer’s disease: protein-lipid interactions and perturbation of signaling. Front Physiol 3:189
154. Susuki K, Baba H, Tohyama K, Kanai K, Kuwabara S et al (2007) Gangliosides contribute to stability of paranodal junctions and ion channel clusters in myelinated nerve fibers. Glia 55:746–757
155. Ohmi Y, Ohkawa Y, Yamauchi Y, Tajima O, Furukawa K (2012) Essential roles of gangliosides in the formation and maintenance of membrane microdomains in brain tissues. Neurochem Res 37:1185–1191