Abstract
Glycosphingolipids are amphiphilic plasma membrane components formed by a glycan linked to a specific lipid moiety. In this chapter we report on these compounds, on their role played in our cells to maintain the correct cell biology.
In detail, we report on their structure, on their metabolic processes, on their interaction with proteins and from this, their property to modulate positively in health and negatively in disease, the cell signaling and cell biology.
Ganglioside nomenclature is in accordance with IUPAC-IUB recommendations (Chester 1998).
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Abe T, Niizuma K, Kanoke A et al (2018) Metabolomic analysis of mouse brain after a transient middle cerebral artery occlusion by mass spectrometry imaging. Neurol Med Chir (Tokyo) 58:384–392. https://doi.org/10.2176/nmc.oa.2018-0054
Alpaugh M, Galleguillos D, Forero J et al (2017) Disease-modifying effects of ganglioside GM1 in Huntington’s disease models. EMBO Mol Med 9:1537–1557. https://doi.org/10.15252/emmm.201707763
Arenz C (2017) Recent advances and novel treatments for sphingolipidoses. Future Med Chem 9:1685–1698
Ariga T, Yu RK (1999) GM1 inhibits amyloid β-protein-induced cytokine release. Neurochem Res 24:219–226. https://doi.org/10.1023/A:1022557920150
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
Bachis A, Rabin SJ, Fiacco MD, Mocchetti I (2002) Gangliosides prevent excitotoxicity through activation of TrkB receptor. Neurotox Res 4:225–234. https://doi.org/10.1080/10298420290015836
Barbacci DC, Roux A, Muller L et al (2017) Mass spectrometric imaging of ceramide biomarkers tracks therapeutic response in traumatic brain injury. ACS Chem Neurosci 8:2266–2274. https://doi.org/10.1021/acschemneuro.7b00189
Bartels T, Kim NC, Luth ES, Selkoe DJ (2014) N-alpha-acetylation of α-synuclein increases its helical folding propensity, GM1 binding specificity and resistance to aggregation. PLoS One 9. https://doi.org/10.1371/journal.pone.0103727
Bergante S, Torretta E, Creo P et al (2014) Gangliosides as a potential new class of stem cell markers: the case of GD1a in human bone marrow mesenchymal stem cells. J Lipid Res 55:549–560. https://doi.org/10.1194/jlr.M046672
Bergante S, Creo P, Piccoli M et al (2018) GM1 ganglioside promotes osteogenic differentiation of human tendon stem cells. Stem Cells Int 2018. https://doi.org/10.1155/2018/4706943
Bernardo A, Harrison FE, McCord M et al (2009) Elimination of GD3 synthase improves memory and reduces amyloid-β plaque load in transgenic mice. Neurobiol Aging 30:1777–1791. https://doi.org/10.1016/j.neurobiolaging.2007.12.022
Bizot V, Cestone E, Michelotti A, Nobile V (2017) Improving skin hydration and age-related symptoms by oral administration of wheat glucosylceramides and digalactosyl diglycerides: a human clinical study. Cosmetics 4:37. https://doi.org/10.3390/cosmetics4040037
Brackman D, Lund-Johansen F, Aarskog D (1995) Expression of leukocyte differentiation antigens during the differentiation of HL-60 cells induced by 1,25-dihydroxyvitamin D3: comparison with the maturation of normal monocytic and granulocytic bone marrow cells. J Leukoc Biol 58:547–555. https://doi.org/10.1002/jlb.58.5.547
Braulke T, Bonifacino JS (2009) Sorting of lysosomal proteins. Biochim Biophys Acta, Mol Cell Res 1793:605–614
Breiden B, Sandhoff K (2018) Ganglioside metabolism and its inherited diseases. In: Methods in molecular biology. Humana Press Inc., Clifton, pp 97–141
Bremer EG, Schlessinger J, Hakomori S (1986) Ganglioside-mediated modulation of cell growth. Specific effects of GM3 on tyrosine phosphorylation of the epidermal growth factor receptor. J Biol Chem 261:2434–2440
Brooksbank BWL, McGovern J (1989) Gangliosides in the brain in adult Down’s syndrome and Alzheimer’s disease. Mol Chem Neuropathol 11:143–156. https://doi.org/10.1007/BF03160048
Brunkhorst R, Friedlaender F, Ferreirós N et al (2015) Alterations of the ceramide metabolism in the peri-infarct cortex are independent of the sphingomyelinase pathway and not influenced by the acid sphingomyelinase inhibitor fluoxetine. Neural Plast 2015:503079
Buccinnà B, Piccinini M, Prinetti A et al (2009) Alterations of myelin-specific proteins and sphingolipids characterize the brains of acid sphingomyelinase-deficient mice, an animal model of Niemann-Pick disease type A. J Neurochem 109:105–115. https://doi.org/10.1111/j.1471-4159.2009.05947.x
Capasso S, Sticco L, Rizzo R et al (2017) Sphingolipid metabolic flow controls phosphoinositide turnover at the trans -Golgi network. EMBO J 36:1736–1754. https://doi.org/10.15252/embj.201696048
Chakrabandhu K, Huault S, Garmy N et al (2008) The extracellular glycosphingolipid-binding motif of Fas defines its internalization route, mode and outcome of signals upon activation by ligand. Cell Death Differ 15:1824–1837. https://doi.org/10.1038/cdd.2008.115
Chang F, Li R, Ladisch S (1997) Shedding of gangliosides by human medulloblastoma cells. Exp Cell Res 234:341–346. https://doi.org/10.1006/excr.1997.3619
Charter HE, Glick FJ, Norris WP, Philips GE (1947) Biochemistry of the sphingolipides: III. Structure of sphingosine. J Biol Chem 170:285–294
Chester MA (1998) IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN). Nomenclature of glycolipids – recommendations 1997. Eur J Biochem 257:293–298. https://doi.org/10.1046/j.1432-1327.1998.2570293.x
Chigorno V, Riva C, Valsecchi M et al (1997) Metabolic processing of gangliosides by human fibroblasts in culture – formation and recycling of separate pools of sphingosine. Eur J Biochem 250:661–669. https://doi.org/10.1111/j.1432-1033.1997.00661.x
Chigorno V, Sciannamblo M, Mikulak J et al (2006) Efflux of sphingolipids metabolically labeled with [1-3H] sphingosine, L-[3-3H]serine and [9,10-3H]palmitic acid from normal cells in culture. Glycoconj J 23:159–165. https://doi.org/10.1007/s10719-006-7921-7
Chiricozzi E, Ciampa MG, Brasile G et al (2015) Direct interaction, instrumental for signaling processes, between LacCer and Lyn in the lipid rafts of neutrophil-like cells. J Lipid Res 56:129–141. https://doi.org/10.1194/jlr.M055319
Chiricozzi E, Pomè DY, Maggioni M et al (2017) Role of the GM1 ganglioside oligosaccharide portion in the TrkA-dependent neurite sprouting in neuroblastoma cells. J Neurochem 143:645–659. https://doi.org/10.1111/jnc.14146
Chiricozzi E, Loberto N, Schiumarini D et al (2018) Sphingolipids role in the regulation of inflammatory response: from leukocyte biology to bacterial infection. J Leukoc Biol 103:445–456
Chiricozzi E, Biase E Di, Maggioni M, et al (2019a) GM1 promotes TrkA-mediated neuroblastoma cell differentiation by occupying a plasma membrane domain different from TrkA. J Neurochem 149:231–241. https://doi.org/10.1111/jnc.14685
Chiricozzi E, Maggioni M, di Biase E, et al (2019b) The neuroprotective role of the GM1 oligosaccharide, II3Neu5Ac-Gg4, in neuroblastoma cells. Mol Neurobiol 56:6673–6702. https://doi.org/10.1007/s12035-019-1556-8
Chiricozzi E, Mauri L, Lunghi G et al (2019c) Parkinson’s disease recovery by GM1 oligosaccharide treatment in the B4galnt1 +/− mouse model. Sci Rep 9. https://doi.org/10.1038/s41598-019-55885-2
Chiricozzi E, Lunghi G, Di Biase E et al (2020) GM1 ganglioside is a key factor in maintaining the mammalian neuronal functions avoiding neurodegeneration. Int J Mol Sci 21
Cohen AW, Razani B, Wang XB et al (2003) Caveolin-1-deficient mice show insulin resistance and defective insulin receptor protein expression in adipose tissue. Am J Physiol Cell Physiol 285. https://doi.org/10.1152/ajpcell.00006.2003
Concolino D, Deodato F, Parini R (2018) Enzyme replacement therapy: efficacy and limitations. Ital J Pediatr 44. https://doi.org/10.1186/s13052-018-0562-1
Coskun Ü, Simons K (2011) Cell membranes: the lipid perspective. Structure 19:1543–1548
Coskun Ü, Grzybek M, Drechsel D, Simons K (2011) Regulation of human EGF receptor by lipids. Proc Natl Acad Sci U S A 108:9044–9048. https://doi.org/10.1073/pnas.1105666108
Crino PB, Ullman MD, Vogt BA et al (1989) Brain gangliosides in dementia of the Alzheimer type. Arch Neurol 46:398–401. https://doi.org/10.1001/archneur.1989.00520400054019
D’Angelo G, Polishchuk E, Tullio G Di, et al (2007) Glycosphingolipid synthesis requires FAPP2 transfer of glucosylceramide. Nature 449:62–67. https://doi.org/10.1038/nature06097
Da Silva JS, Hasegawa T, Miyagi T et al (2005) Asymmetric membrane ganglioside sialidase activity specifies axonal fate. Nat Neurosci 8:606–615. https://doi.org/10.1038/nn1442
Dai R, Zhang S, Duan W et al (2017) Enhanced autophagy contributes to protective effects of GM1 ganglioside against Aβ1-42-induced neurotoxicity and cognitive deficits. Neurochem Res 42:2417–2426. https://doi.org/10.1007/s11064-017-2266-0
De Girolamo LA, Hargreaves AJ, Ellen Billett E (2001) Protection from MPTP-induced neurotoxicity in differentiating mouse N2a neuroblastoma cells. J Neurochem 76:650–660. https://doi.org/10.1046/j.1471-4159.2001.00066.x
Del Tredici R, Vos D et al (2002) Where does Parkinson disease pathology begin in the brain? J Neuropathol Exp Neurol 61. https://doi.org/10.1093/JNEN/61.5.413
Deng W, Li R, Ladisch S (2000) Influence of cellular ganglioside depletion on tumor formation. J Natl Cancer Inst 92:912–917
Desai BS, Monahan AJ, Carvey PM, Hendey B (2007) Blood-brain barrier pathology in Alzheimer’s and Parkinson’s disease: implications for drug therapy. In: Cell transplantation. Cognizant Communication Corporation, Amsterdam, pp 285–299
Desplats PA, Denny CA, Kass KE et al (2007) Glycolipid and ganglioside metabolism imbalances in Huntington’s disease. Neurobiol Dis 27:265–277. https://doi.org/10.1016/j.nbd.2007.05.003
Di Biase E, Lunghi G, Fazzari M et al (2020a) Gangliosides in the differentiation process of primary neurons: the specific role of GM1-oligosaccharide. Glycoconj J:329–343. https://doi.org/10.1007/s10719-020-09919-x
Di Biase E, Lunghi G, Maggioni M et al (2020b) GM1 oligosaccharide crosses the human blood-brain barrier in vitro by a paracellular route. Int J Mol Sci 21. https://doi.org/10.3390/ijms21082858
Di Pardo A, Maglione V (2018) Sphingolipid metabolism: a new therapeutic opportunity for brain degenerative disorders. Front Neurosci 12
Di Pardo A, Maglione V, Alpaugh M et al (2012) Ganglioside GM1 induces phosphorylation of mutant huntingtin and restores normal motor behavior in Huntington disease mice. Proc Natl Acad Sci U S A 109:3528–3533. https://doi.org/10.1073/pnas.1114502109
Doherty GJ, McMahon HT (2009) Mechanisms of endocytosis. Annu Rev Biochem 78:857–902. https://doi.org/10.1146/annurev.biochem.78.081307.110540
Duchemin AM, Ren Q, Mo L et al (2002) GM1 ganglioside induces phosphorylation and activation of Trk and Erk in brain. J Neurochem 81:696–707. https://doi.org/10.1046/j.1471-4159.2002.00831.x
Duchemin AM, Ren Q, Neff NH, Hadjiconstantinou M (2008) GM1-induced activation of phosphatidylinositol 3-kinase: involvement of Trk receptors. J Neurochem 104:1466–1477. https://doi.org/10.1111/j.1471-4159.2007.05088.x
Erdö F, Denes L, De Lange E (2017) Age-associated physiological and pathological changes at the blood-brain barrier: a review. J Cereb Blood Flow Metab 37:4–24
Fantini J, Yahi N (2015) Lipid regulation of receptor function. In: Brain lipids in synaptic function and neurological disease, first edit. Elsevier, San Diego, pp 163–181
Farfel-Becker T, Vitner EB, Kelly SL et al (2014) Neuronal accumulation of glucosylceramide in a mouse model of Neuronopathic Gaucher disease leads to neurodegeneration. Hum Mol Genet 23:843–854
Farooqui T, Franklin T, Pearl DK, Yates AJ (1997) Ganglioside GM1 enhances induction by nerve growth factor of a putative dimer of TrkA. J Neurochem 68:2348–2355. https://doi.org/10.1046/j.1471-4159.1997.68062348.x
Fazzari M, Audano M, Lunghi G et al (2020) The oligosaccharide portion of ganglioside GM1 regulates mitochondrial function in neuroblastoma cells. Glycoconj J 37:293–306. https://doi.org/10.1007/s10719-020-09920-4
Feingold KR, Elias PM (2014) Role of lipids in the formation and maintenance of the cutaneous permeability barrier. Biochim Biophys Acta Mol Cell Biol Lipids 1841:280–294
Ferlinz K, Kopal G, Bernardo K et al (2001) Human acid ceramidase: processing, glycosylation, and lysosomal targeting. J Biol Chem 276:35352–35360. https://doi.org/10.1074/jbc.M103066200
Ferrari G, Anderson BL, Stephens RM et al (1995) Prevention of apoptotic neuronal death by G(M1) ganglioside. Involvement of Trk neurotrophin receptors. J Biol Chem 270:3074–3080. https://doi.org/10.1074/jbc.270.7.3074
Ferrucci L, Gonzalez-Freire M, Fabbri E et al (2020) Measuring biological aging in humans: a quest. Aging Cell 19
Filocamo M, Morrone A (2011) Lysosomal storage disorders: molecular basis and laboratory testing. Hum Genomics 5:156–169
Flatt T (2012) A new definition of aging? Front Genet 3:1–2
Futerman AH, Van Meer G (2004) The cell biology of lysosomal storage disorders. Nat Rev Mol Cell Biol 5:554–565
Futerman AH, Sussman JL, Horowitz M et al (2004) New directions in the treatment of Gaucher disease. Trends Pharmacol Sci 25:147–151. https://doi.org/10.1016/j.tips.2004.01.004
Gabandé-Rodríguez E, Boya P, Labrador V et al (2014) High sphingomyelin levels induce lysosomal damage and autophagy dysfunction in Niemann Pick disease type A. Cell Death Differ 21:864–875. https://doi.org/10.1038/cdd.2014.4
Ghadially R, Brown BE, Sequeira-Martin SM et al (1995) The aged epidermal permeability barrier. Structural, functional, and lipid biochemical abnormalities in humans and a senescent murine model. J Clin Invest 95:2281–2290. https://doi.org/10.1172/JCI117919
Ghidoni R, Trinchera M, Venerando B et al (1986) Incorporation and metabolism of exogenous G(M1) ganglioside in rat liver. Biochem J 237:147–155. https://doi.org/10.1042/bj2370147
Ghosh P, Dahms NM, Kornfeld S (2003) Mannose 6-phosphate receptors: new twists in the tale. Nat Rev Mol Cell Biol 4:202–212
Gladyshev VN (2016) Aging: progressive decline in fitness due to the rising deleteriome adjusted by genetic, environmental, and stochastic processes. Aging Cell 15:594–602
Grassi S, Chiricozzi E, Mauri L et al (2019) Sphingolipids and neuronal degeneration in lysosomal storage disorders. J Neurochem 148:600–611. https://doi.org/10.1111/jnc.14540
Grösch S, Schiffmann S, Geisslinger G (2012) Chain length-specific properties of ceramides. Prog Lipid Res 51:50–62
Gu LZ, Huang BS, Shen W et al (2013) Early activation of nSMase2/ceramide pathway in astrocytes is involved in ischemia-associated neuronal damage via inflammation in rat hippocampi. J Neuroinflam 10. https://doi.org/10.1186/1742-2094-10-109
Hadaczek P, Wu G, Sharma N et al (2015) GDNF signaling implemented by GM1 ganglioside; failure in Parkinson’s disease and GM1-deficient murine model. Exp Neurol 263:177–189. https://doi.org/10.1016/j.expneurol.2014.10.010
Hadjiconstantinou M, Mariani AP, Neff NH (1989) GM1 ganglioside-induced recovery of nigrostriatal dopaminergic neurons after MPTP: an immunohistochemical study. Brain Res 484:297–303. https://doi.org/10.1016/0006-8993(89)90373-9
Hakomori S (1985) Aberrant glycosylation in cancer cell membranes as focused on glycolipids: overview and perspectives. Cancer Res 45:2405–2414
Hakomori S-I (1989) Aberrant glycosylation in tumors and tumor-associated carbohydrate antigens. Adv Cancer Res 52:257–331. https://doi.org/10.1016/S0065-230X(08)60215-8
Hakomori SI (1996) Tumor malignancy defined by aberrant glycosylation and sphingo(glyco)lipid metabolism. Cancer Res 56:5309–5318
Hakomori S (2002) Glycosylation defining cancer malignancy: new wine in an old bottle. Proc Natl Acad Sci U S A 99:10231–10233
Hakomori SI, Igarashi Y (1995) Functional role of glycosphingolipids in cell recognition and signaling. J Biochem 118:1091–1103. https://doi.org/10.1093/oxfordjournals.jbchem.a124992
Hakomori SI, Handa K, Iwabuchi K et al (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 [1]. Glycobiology 8
Hallett PJ, Huebecker M, Brekk OR et al (2018) Glycosphingolipid levels and glucocerebrosidase activity are altered in normal aging of the mouse brain. Neurobiol Aging 67:189–200. https://doi.org/10.1016/j.neurobiolaging.2018.02.028
Haughey NJ (2010) Sphingolipids in neurodegeneration. NeuroMolecular Med 12:301–305
Hayashi H, Kimura N, Yamaguchi H et al (2004) A seed for Alzheimer amyloid in the brain. J Neurosci 24:4894–4902. https://doi.org/10.1523/JNEUROSCI.0861-04.2004
Hein LK, Duplock S, Hopwood JJ, Fuller M (2008) Lipid composition of microdomains is altered in a cell model of Gaucher disease. J Lipid Res 49:1725–1734. https://doi.org/10.1194/jlr.M800092-JLR200
Hemler ME (1998) Integrin associated proteins. Curr Opin Cell Biol 10:578–585. https://doi.org/10.1016/S0955-0674(98)80032-X
Hernández-Corbacho MJ, Jenkins RW, Clarke CJ et al (2011) Accumulation of long-chain glycosphingolipids during aging is prevented by caloric restriction. PLoS One 6. https://doi.org/10.1371/journal.pone.0020411
Herrero MT, Perez-Otaño I, Oset C et al (1993) GM-1 ganglioside promotes the recovery of surviving midbrain dopaminergic neurons in MPTP-treated monkeys. Neuroscience 56:965–972. https://doi.org/10.1016/0306-4522(93)90142-3
Hikita T, Tadano-Aritomi K, Iida-Tanaka N et al (2002) Cationic glycosphingolipids in neuronal tissues and their possible biological significance. Neurochem Res 27:575–581. https://doi.org/10.1023/A:1020259630034
Holleran WM, Takagi Y, Uchida Y (2006) Epidermal sphingolipids: metabolism, function, and roles in skin disorders. FEBS Lett 580:5456–5466
Horres CR, Hannun YA (2012) The roles of neutral sphingomyelinases in neurological pathologies. Neurochem Res 37:1137–1149
Iwabuchi K, Nagaoka I (2002) Lactosylceramide-enriched glycosphingolipid signaling domain mediates superoxide generation from human neutrophils. Blood 100
Iwabuchi K, Handa K, Hakomori SI (1998) Separation of “glycosphingolipid signaling domain” from caveolin- containing membrane fraction in mouse melanoma B16 cells and its role in cell adhesion coupled with signaling. J Biol Chem 273:33766–33773. https://doi.org/10.1074/jbc.273.50.33766
Iwabuchi K, Prinetti A, Sonnino S et al (2008) Involvement of very long fatty acid-containing lactosylceramide in lactosylceramide-mediated superoxide generation and migration in neutrophils. Glycoconj J 25:357–374. https://doi.org/10.1007/s10719-007-9084-6
Jakóbkiewicz-Banecka J, Gabig-Cimińska M, Banecka-Majkutewicz Z et al (2014) Factors and processes modulating phenotypes in neuronopathic lysosomal storage diseases. Metab Brain Dis 29:1–8
Jones ZB, Ren Y (2016) Sphingolipids in spinal cord injury. Int J Physiol Pathophysiol Pharmacol 8:52–69
Kabayama K, Sato T, Saito K et al (2007) Dissociation of the insulin receptor and caveolin-1 complex by ganglioside GM3 in the state of insulin resistance. Proc Natl Acad Sci U S A 104:13678–13683. https://doi.org/10.1073/pnas.0703650104
Kanoh H, Nitta T, Go S et al (2020) Homeostatic and pathogenic roles of GM 3 ganglioside molecular species in TLR 4 signaling in obesity. EMBO J 39. https://doi.org/10.15252/embj.2019101732
Kawakami Y, Kawakami K, Steelant WFA et al (2002) Tetraspanin CD9 is a “proteolipid,” and its interaction with α3 integrin in microdomain is promoted by GM3 ganglioside, leading to inhibition of laminin-5-dependent cell motility. J Biol Chem 277:34349–34358. https://doi.org/10.1074/jbc.M200771200
Kawamura S, Ohyama C, Watanabe R et al (2001) Glycolipid composition in bladder tumor: a crucial role of gm3 ganglioside in tumor invasion. Int J Cancer 94:343–347. https://doi.org/10.1002/ijc.1482
Kawashima N, Yoon SJ, Itoh K, Nakayama KI (2009) Tyrosine kinase activity of epidermal growth factor receptor is regulated by GM3 binding through carbohydrate to carbohydrate interactions. J Biol Chem 284:6147–6155. https://doi.org/10.1074/jbc.M808171200
Kim SM, Jung JU, Ryu JS et al (2008) Effects of gangliosides on the differentiation of human mesenchymal stem cells into osteoblasts by modulating epidermal growth factor receptors. Biochem Biophys Res Commun 371:866–871. https://doi.org/10.1016/j.bbrc.2008.04.162
Kischkel FC, Hellbardt S, Behrmann I et al (1995) Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a Death-Inducing Signaling Complex (DISC) with the receptor. EMBO J 14:5579–5588
Kishimoto Y, Hiraiwa M, O’Brien JS (1992) Saposins: structure, function, distribution, and molecular genetics. J Lipid Res 33:1255–1267
Kitatani K, Idkowiak-Baldys J, Hannun YA (2008) The sphingolipid salvage pathway in ceramide metabolism and signaling. Cell Signal 20:1010–1018
Kniep B, Skubitz KM (1998) Subcellular localization of glycosphingolipids in human neutrophils. J Leukoc Biol 63:83–88. https://doi.org/10.1002/jlb.63.1.83
Kojima N, Shiota M, Sadahira Y et al (1992) Cell adhesion in a dynamic flow system as compared to static system. Glycosphingolipid-glycosphingolipid interaction in the dynamic system predominates over lectin- or integrin-based mechanisms in adhesion of B16 melanoma cells to non-activated endothelial cells. J Biol Chem 267:17264–17270
Kolter T, Sandhoff K (2005) Principles of lysosomal membrane digestion: stimulation of sphingolipid degradation by sphingolipid activator proteins and anionic lysosomal lipids. Annu Rev Cell Dev Biol 21:81–103. https://doi.org/10.1146/annurev.cellbio.21.122303.120013
Kolter T, Sandhoff K (2006) Sphingolipid metabolism diseases. Biochim Biophys Acta Biomembr 1758:2057–2079
Kracun I, Rosner H, Drnovsek V et al (1991) Human brain gangliosides in development, aging and disease. Int J Dev Biol 35:289–295. https://doi.org/10.1387/ijdb.1814411
Kracun I, Kalanj S, Talan-Hranilovic J, Cosovic C (1992) Cortical distribution of gangliosides in Alzheimer’s disease. Neurochem Int 20:433–438. https://doi.org/10.1016/0197-0186(92)90058-Y
Kreutz F, Frozza RL, Breier AC et al (2011) Amyloid-β induced toxicity involves ganglioside expression and is sensitive to GM1 neuroprotective action. Neurochem Int 59:648–655. https://doi.org/10.1016/j.neuint.2011.06.007
Ladisch S, Kitada S, Hays EF (1987) Gangliosides shed by tumor cells enhance tumor formation in mice. J Clin Invest 79:1879–1882. https://doi.org/10.1172/JCI113031
Ladisch S, Li R, Olson E (1994) Ceramide structure predicts tumor ganglioside immunosuppressive activity. Proc Natl Acad Sci U S A 91:1974–1978. https://doi.org/10.1073/pnas.91.5.1974
Ladisch S, Chang F, Li R et al (1997) Detection of medulloblastoma and astrocytoma-associated, ganglioside G(D3) in cerebrospinal fluid. Cancer Lett 120:71–78. https://doi.org/10.1016/S0304-3835(97)00297-8
Langeveld M, Ghauharali KJM, Sauerwein HP et al (2008) Type I Gaucher disease, a glycosphingolipid storage disorder, is associated with insulin resistance. J Clin Endocrinol Metab 93:845–851. https://doi.org/10.1210/jc.2007-1702
Ledeen R, Wu G (2018a) Gangliosides of the nervous system. In: Methods in molecular biology. Humana Press Inc, New York, pp 19–55
Ledeen RW, Wu G (2018b) Gangliosides, α-Synuclein, and Parkinson’s disease. In: Progress in molecular biology and translational science. Elsevier, Oxford, pp 435–454
Ledesma MD, Martin MG, Dotti CG (2012) Lipid changes in the aged brain: effect on synaptic function and neuronal survival. Prog Lipid Res 51:23–35
Lee KH, Feig C, Tchikov V et al (2006) The role of receptor internalization in CD95 signaling. EMBO J 25:1009–1023. https://doi.org/10.1038/sj.emboj.7601016
Li M (2018) Enzyme replacement therapy: a review and its role in treating lysosomal storage diseases. Pediatr Ann 47:e191–e197. https://doi.org/10.3928/19382359-20180424-01
Lill CM, Roehr JT, McQueen MB et al (2009) The PDGene database. Alzheimer Research Forum. Available at: http://www.pdgene.org2
Lu C, Ferzly M, Takagi J, Springer TA (2001) Epitope mapping of antibodies to the C-terminal region of the integrin β 2 subunit reveals regions that become exposed upon receptor activation. J Immunol 166:5629–5637. https://doi.org/10.4049/jimmunol.166.9.5629
Maceyka M, Harikumar KB, Milstien S, Spiegel S (2012) Sphingosine-1-phosphate signaling and its role in disease. Trends Cell Biol 22:50–60
Magistretti PJ, Geisler FH, Schneider JS et al (2019) Gangliosides: treatment avenues in neurodegenerative disease. Front Neurol 10
Maglione V, Marchi P, Di Pardo A et al (2010) Impaired ganglioside metabolism in Huntington’s disease and neuroprotective role of GM1. J Neurosci 30:4072–4080. https://doi.org/10.1523/JNEUROSCI.6348-09.2010
Marquina G, Waki H, Fernandez LE et al (1996) Gangliosides expressed in human breast cancer. Cancer Res 56:5165–5171
Martinez Z, Zhu M, Han S, Fink AL (2007) GM1 specifically interacts with α-synuclein and inhibits fibrillation. Biochemistry 46:1868–1877. https://doi.org/10.1021/bi061749a
Mayor S, Pagano RE (2007) Pathways of clathrin-independent endocytosis. Nat Rev Mol Cell Biol 8:603–612
Mazzulli JR, Xu YH, Sun Y et al (2011) Gaucher disease glucocerebrosidase and α-synuclein form a bidirectional pathogenic loop in synucleinopathies. Cell 146:37–52. https://doi.org/10.1016/j.cell.2011.06.001
McNeill A, Magalhaes J, Shen C et al (2014) Ambroxol improves lysosomal biochemistry in Glucocerebrosidase mutation-linked Parkinson disease cells. Brain 137:1481–1495
Mencarelli C, Martinez-Martinez P (2013) Ceramide function in the brain: when a slight tilt is enough. Cell Mol Life Sci 70:181–203
Meredith GE, Rademacher DJ (2011) MPTP mouse models of Parkinson’s disease: an update. J Parkinsons Dis 1:19–33
Merrill AH (2011) Sphingolipid and glycosphingolipid metabolic pathways in the era of sphingolipidomics. Chem Rev 111:6387–6422
Mielke MM, Lyketsos CG (2010) Alterations of the sphingolipid pathway in Alzheimer’s disease: new biomarkers and treatment targets? NeuroMolecular Med 12:331–340
Miljan EA, Bremer EG (2002) Regulation of growth factor receptors by gangliosides. Sci STKE 2002:re15
Miljan EA, Meuillet EJ, Mania-Farnell B et al (2002) Interaction of the extracellular domain of the epidermal growth factor receptor with gangliosides. J Biol Chem 277:10108–10113. https://doi.org/10.1074/jbc.M111669200
Mitsuzuka K, Handa K, Satoh M et al (2005) A specific microdomain (“glycosynapse 3”) controls phenotypic conversion and reversion of bladder cancer cells through GM3-mediated interaction of α3β1 integrin with CD9. J Biol Chem 280:35545–35553. https://doi.org/10.1074/jbc.M505630200
Miura Y, Kainuma M, Jiang H et al (2004) Reversion of the Jun-induced oncogenic phenotype by enhanced synthesis of sialosyllactosylceramide (GM3 ganglioside). Proc Natl Acad Sci U S A 101:16204–16209. https://doi.org/10.1073/pnas.0407297101
Mo L, Ren Q, Duchemin AM et al (2005) GM1 and ERK signaling in the aged brain. Brain Res 1054:125–134. https://doi.org/10.1016/j.brainres.2005.06.068
Mutoh T, Tokuda A, Miyadai T et al (1995) Ganglioside GM1 binds to the Trk protein and regulates receptor function. Proc Natl Acad Sci U S A 92:5087–5091. https://doi.org/10.1073/pnas.92.11.5087
Mutoh T, Hamano T, Yano S et al (2002) Stable transfection of GM1 synthase gene into GM1-deficient NG108-15 cells, CR-72 cells, rescues the responsiveness of Trk-neurotrophin receptor to its ligand, NGF. Neurochem Res 27:801–806. https://doi.org/10.1023/A:1020209008169
Nakayama H, Yoshizaki F, Prinetti A et al (2008) Lyn-coupled LacCer-enriched lipid rafts are required for CD11b/CD18-mediated neutrophil phagocytosis of nonopsonized microorganisms. J Leukoc Biol 83:728–741. https://doi.org/10.1189/jlb.0707478
Nakayama H, Ogawa H, Takamori K, Iwabuchi K (2013) GSL-enriched membrane microdomains in innate immune responses. Arch Immunol Ther Exp 61:217–228
Neudorfer O, Giladi N, Elstein D et al (1996) Occurrence of Parkinson’s syndrome in Type I Gaucher disease. QJM 89:691–694
Ngamukote S, Yanagisawa M, Ariga T et al (2007) Developmental changes of glycosphingolipids and expression of glycogenes in mouse brains. J Neurochem 103:2327–2341. https://doi.org/10.1111/j.1471-4159.2007.04910.x
Nicotra A, Parvez SH (2002) Apoptotic molecules and MPTP-induced cell death. Neurotoxicol Teratol 24:599–605
Nojiri H, Stroud M, Hakomori S (1991) A specific type of ganglioside as a modulator of insulin-dependent cell growth and insulin receptor tyrosine kinase activity. Possible Association of Ganglioside-Induced Inhibition of insulin receptor function and monocytic differentiation induction in HL-60 cells. J Biol Chem 266:4531–4537
Nojiri H, Yamana H, Shirouzu G et al (2002) Glycotherapy for cancer: remodeling of ganglioside pattern as an effective approach for cancer therapy. Cancer Detect Prev 26:114–120. https://doi.org/10.1016/S0361-090X(02)00033-8
Novgorodov SA, Gudz TI (2009) Ceramide and mitochondria in ischemia/reperfusion. J Cardiovasc Pharmacol 53:198–208. https://doi.org/10.1097/FJC.0b013e31819b52d5
Ohsawa T (1989) Changes of mouse brain gangliosides during aging from young adult until senescence. Mech Ageing Dev 50:169–177. https://doi.org/10.1016/0047-6374(89)90012-2
Ohyama C, Orikasa S, Kawamura S et al (1996) Galactosylgloboside expression in seminoma. Inverse correlation with metastatic potential. Cancer 76. https://doi.org/10.1002/1097-0142(19950915)76:6<1043::AID-CNCR2820760619>3.0.CO;2-A
Ong WY, Herr DR, Farooqui T et al (2015) Role of sphingomyelinases in neurological disorders. Expert Opin Ther Targets 19:1725–1742
Ono M, Handa K, Withers DA, Hakomori S (1999) Motility inhibition and apoptosis are induced by metastasis-suppressing gene product CD82 and its analogue CD9, with concurrent glycosylation. Cancer Res 59:2335–2339
Ono M, Handa K, Sonnino S et al (2001) GM3 ganglioside inhibits CD9-facilitated haptotactic cell motility: Coexpression of GM3 and CD9 is essential in the downregulation of tumor cell motility and malignancy. Biochemistry 40:6414–6421. https://doi.org/10.1021/bi0101998
Ortiz A, Germain DP, Desnick RJ et al (2018) Fabry disease revisited: management and treatment recommendations for adult patients. Mol Genet Metab 123:416–427
Parenti G, Andria G, Ballabio A (2015) Lysosomal storage diseases: from pathophysiology to therapy. Annu Rev Med 66:471–486. https://doi.org/10.1146/annurev-med-122313-085916
Perera RM, Zoncu R (2016) The lysosome as a regulatory hub. Annu Rev Cell Dev Biol 32:223–253. https://doi.org/10.1146/annurev-cellbio-111315-125125
Perry RJ, Ridgway ND (2005) Molecular mechanisms and regulation of ceramide transport. Biochim Biophys Acta Mol Cell Biol Lipids 1734:220–234
Piccinini M, Scandroglio F, Prioni S et al (2010) Deregulated sphingolipid metabolism and membrane organization in neurodegenerative disorders. Mol Neurobiol 41:314–340. https://doi.org/10.1007/s12035-009-8096-6
Pitto M, Mutoh T, Kuriyama M et al (1998) Influence of endogenous GM1 ganglioside on TrkB activity, in cultured neurons. FEBS Lett 439:93–96. https://doi.org/10.1016/S0014-5793(98)01344-1
Platt F, Boland B, van der Spoel AC (2012) The cell biology of disease: lysosomal storage disorders: the cellular impact of lysosomal dysfunction. J Cell Biol 199:723–734
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. https://doi.org/10.1007/BF03160083
Prinetti A, Iwabuchi K, Hakomori SI (1999) Glycosphingolipid-enriched signaling domain in mouse neuroblastoma Neuro2a cells. Mechanism of ganglioside-dependent neuritogenesis. J Biol Chem 274:20916–20924. https://doi.org/10.1074/jbc.274.30.20916
Prinetti A, Chigorno V, Tettamanti G, Sonnino S (2000) Sphingolipid-enriched membrane domains from rat cerebellar granule cells differentiated in culture: a compositional study. J Biol Chem 275:11658–11665. https://doi.org/10.1074/jbc.275.16.11658
Prinetti A, Loberto N, Chigorno V, Sonnino S (2009) Glycosphingolipid behaviour in complex membranes. Biochim Biophys Acta Biomembr 1788:184–193
Rabin SJ, Mocchetti I (1995) GM1 ganglioside activates the high-affinity nerve growth factor receptor trkA. J Neurochem 65:347–354. https://doi.org/10.1046/j.1471-4159.1995.65010347.x
Reczek D, Schwake M, Schröder J et al (2007) LIMP-2 is a receptor for lysosomal mannose-6-phosphate-independent targeting of β-glucocerebrosidase. Cell 131:770–783. https://doi.org/10.1016/j.cell.2007.10.018
Revel-Vilk S, Szer J, Mehta A, Zimran A (2018) How we manage Gaucher disease in the era of choices. Br J Haematol 182:467–480
Riboldi GM, Di Fonzo AB (2019) GBA, Gaucher disease, and Parkinson’s disease: from genetic to clinic to new therapeutic approaches. Cell 8:364. https://doi.org/10.3390/cells8040364
Riboni L, Bassi R, Prinetti A, Tettamanti G (1996) Salvage of catabolic products in ganglioside metabolism: a study on rat cerebellar granule cells in culture. FEBS Lett 391:336–340. https://doi.org/10.1016/0014-5793(96)00772-7
Ringerike T, Blystad FD, Levy FO et al (2002) Cholesterol is important in control of EGF receptor kinase activity but EGF receptors are not concentrated in caveolae. J Cell Sci 115:1331–1340
Rocha EM, Smith GA, Park E et al (2015) Progressive decline of glucocerebrosidase in aging and Parkinson’s disease. Ann Clin Transl Neurol 2:433–438. https://doi.org/10.1002/acn3.177
Roepstorff K, Thomsen P, Sandvig K, Van Deurs B (2002) Sequestration of epidermal growth factor receptors in non-caveolar lipid rafts inhibits ligand binding. J Biol Chem 277:18954–18960. https://doi.org/10.1074/jbc.M201422200
Rogers J, Harding C, Mayo A et al (1996) Stratum corneum lipids: the effect of ageing and the seasons. Arch Dermatol Res 288:765–770. https://doi.org/10.1007/BF02505294
Rothblat DS, Schneider JS (1998) Effects of GM1 ganglioside treatment on dopamine innervation of the striatum of MPTP-treated mice. In: Annals of the New York Academy of Sciences. Blackwell Publishing Inc, pp 274–277
Roux A, Muller L, Jackson SN et al (2016) Mass spectrometry imaging of rat brain lipid profile changes over time following traumatic brain injury. J Neurosci Methods 272:19–32. https://doi.org/10.1016/j.jneumeth.2016.02.004
Russo D, Parashuraman S, D’Angelo G (2016) Glycosphingolipid–protein interaction in signal transduction. Int J Mol Sci 17:1732
Saftig P, Klumperman J (2009) Lysosome biogenesis and lysosomal membrane proteins: trafficking meets function. Nat Rev Mol Cell Biol 10:623–635
Sajja VSSS, Jablonska A, Haughey N et al (2018) Sphingolipids and microRNA changes in blood following blast traumatic brain injury: an exploratory study. J Neurotrauma 35:353–361. https://doi.org/10.1089/neu.2017.5009
Samarani M, Loberto N, Soldà G et al (2018) A lysosome–plasma membrane–sphingolipid axis linking lysosomal storage to cell growth arrest. FASEB J 32:5685–5702. https://doi.org/10.1096/fj.201701512RR
Sandhoff K (2016) Neuronal sphingolipidoses: membrane lipids and sphingolipid activator proteins regulate lysosomal sphingolipid catabolism. Biochimie 130:146–151
Sasaki N, Itakura Y, Toyoda M (2015) Ganglioside GM1 contributes to the state of insulin resistance in senescent human arterial endothelial cells. J Biol Chem 290:25475–25486. https://doi.org/10.1074/jbc.M115.684274
Satoh M, Handa K, Saito S et al (1996) Disialosyl galactosylgloboside as an adhesion molecule expressed on renal cell carcinoma and its relationship to metastatic potential. Cancer Res 56:1932–1938
Satoh M, Nejad FM, Ohtani H et al (2000) Association of renal cell carcinoma antigen, disialylgalactosylgloboside, with c-Src and Rho A in clustered domains at the surface membrane. Int J Oncol 16:529–536. https://doi.org/10.3892/ijo.16.3.529
Satoh M, Ito A, Nojiri H et al (2001) Enhanced GM3 expression, associated with decreased invasiveness, is induced by Brefeldin A in bladder cancer cells. Int J Oncol 19:723–731
Saulino MF, Schengrund C-L (1994) Differential accumulation of gangliosides by the brains of MPTP-lesioned mice. J Neurosci Res 37:384–391. https://doi.org/10.1002/jnr.490370310
Scandroglio F, Venkata JK, Loberto N et al (2008) Lipid content of brain, brain membrane lipid domains, and neurons from acid sphingomyelinase deficient mice. J Neurochem 107:329–338. https://doi.org/10.1111/j.1471-4159.2008.05591.x
Schengrund CL (2015) Gangliosides: glycosphingolipids essential for normal neural development and function. Trends Biochem Sci 40:397–406
Schengrund C-L, Prouty C (1988) Oligosaccharide portion of GM1 enhances process formation by S20Y neuroblastoma cells. J Neurochem 51:277–282. https://doi.org/10.1111/j.1471-4159.1988.tb04867.x
Schnaar RL (2016) Gangliosides of the vertebrate nervous system. J Mol Biol 428:3325–3336
Schneider JS (2018) Altered expression of genes involved in ganglioside biosynthesis in substantia nigra neurons in Parkinson’s disease. PLoS One 13. https://doi.org/10.1371/journal.pone.0199189
Schneider JS, DiStefano L (1994) Oral administration of semisynthetic sphingolipids promotes recovery of striatal dopamine concentrations in a murine model of parkinsonism. Neurology 44:748–750. https://doi.org/10.1212/wnl.44.4.748
Schneider JS, Pope A, Simpson K et al (1992) Recovery from experimental parkinsonism in primates with GM1 ganglioside treatment. Science 256:843–846. https://doi.org/10.1126/science.1350379
Schneider JS, Sendek S, Daskalakis C, Cambi F (2010) GM1 ganglioside in Parkinson’s disease: results of a five year open study. J Neurol Sci 292:45–51. https://doi.org/10.1016/j.jns.2010.02.009
Schneider JS, Gollomp SM, Sendek S et al (2013) A randomized, controlled, delayed start trial of GM1 ganglioside in treated Parkinson’s disease patients. J Neurol Sci 324:140–148. https://doi.org/10.1016/j.jns.2012.10.024
Schneider JS, Cambi F, Gollomp SM et al (2015a) GM1 ganglioside in Parkinson’s disease: pilot study of effects on dopamine transporter binding. J Neurol Sci 356:118–123. https://doi.org/10.1016/j.jns.2015.06.028
Schneider JS, Seyfried TN, Choi HS, Kidd SK (2015b) Intraventricular sialidase administration enhances GM1 ganglioside expression and is partially neuroprotective in a mouse model of Parkinson’s disease. PLoS One 10. https://doi.org/10.1371/journal.pone.0143351
Schneider JS, Aras R, Williams CK et al (2019) GM1 ganglioside modifies α-Synuclein toxicity and is neuroprotective in a rat α-Synuclein model of Parkinson’s disease. Sci Rep 9. https://doi.org/10.1038/s41598-019-42847-x
Schuchman EH (2007) The pathogenesis and treatment of acid sphingomyelinase-deficient Niemann-Pick disease. J Inherit Metab Dis 30:654–663
Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT (2011) Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med 1. https://doi.org/10.1101/cshperspect.a006189
Settembre C, Fraldi A, Medina DL, Ballabio A (2013) Signals from the lysosome: a control centre for cellular clearance and energy metabolism. Nat Rev Mol Cell Biol 14:283–296
Sidransky E (2005) Gaucher disease and parkinsonism. Mol Genet Metab 84:302–304
Sidransky E, Lopez G (2012) The link between the GBA gene and parkinsonism. Lancet Neurol 11:986–998. https://doi.org/10.1016/S1474-4422(12)70190-4
Simons K, Ikonen E (1997) Functional rafts in cell membranes. Nature 387:569–572
Simons K, Toomre D (2000) Lipid rafts and signal transduction. Nat Rev Mol Cell Biol 1:31–39
Sokolova TV, Zakharova IO, Furaev VV et al (2007) Neuroprotective effect of ganglioside GM1 on the cytotoxic action of hydrogen peroxide and amyloid β-peptide in PC12 cells. Neurochem Res 32:1302–1313. https://doi.org/10.1007/s11064-007-9304-2
Sokolova T, Rychkova MP, Avrova N (2014) Protective effect of GM1 ganglioside against toxic action of glutamate on cerebellar granule cells. J Evol Biochem Physiol 50:399–401
Sonderfeld S, Conzelma E, Schwarzmann G et al (1985) Incorporation and metabolism of ganglioside GM2 in skin fibroblasts from normal and GM2 gangliosidosis subjects. Eur J Biochem 149:247–255. https://doi.org/10.1111/j.1432-1033.1985.tb08919.x
Sonnino S, Prinetti A (2013) Membrane domains and the “lipid raft” concept. Curr Med Chem 20:4–21
Sonnino S, Ghidoni R, Marchesini S, Tettamanti G (1979) Cytosolic gangliosides: occurrence in calf brain as ganglioside-protein complexes. J Neurochem 33:117–121. https://doi.org/10.1111/j.1471-4159.1979.tb11713.x
Sonnino S, Prinetti A, Mauri L et al (2006) Dynamic and structural properties of sphingolipids as driving forces for the formation of membrane domains. Chem Rev 106:2111–2125
Sonnino S, Chiricozzi E, Ciampa MG et al (2017) Serum antibodies to glycans in peripheral neuropathies. Mol Neurobiol 54:1564–1567
Spassieva S, Bieberich E (2016) Lysosphingolipids and sphingolipidoses: Psychosine in Krabbe’s disease. J Neurosci Res 94:974–981
Spychalska J, Smoleńska-Sym G, Zdebska E et al (2003) Quantitative analysis of LacCer/CDw17 in human myelogenous leukaemic cells. Cell Mol Biol Lett 8:911–917
Steelant WF, Kawakami Y, Ito A et al (2002) Monosialyl-Gb5 organized with cSrc and FAK in GEM of human breast carcinoma MCF-7 cells defines their invasive properties. FEBS Lett 531:93–98. https://doi.org/10.1016/S0014-5793(02)03484-1
Stern MB, Lang A, Poewe W (2012) Toward a redefinition of Parkinson’s disease. Mov Disord 27:54–60
Stoffel W (1970) Studies on the biosynthesis and degradation of sphingosine bases. Chem Phys Lipids 5:139–158. https://doi.org/10.1016/0009-3084(70)90014-9
Sugiura Y, Shimma S, Konishi Y et al (2008) Imaging mass spectrometry technology and application on ganglioside study; visualization of age-dependent accumulation of C20-ganglioside molecular species in the mouse hippocampus. PLoS One 3. https://doi.org/10.1371/journal.pone.0003232
Svennerholm L (1994) Ganglioside loss is a primary event in Alzheimer disease type I. Prog Brain Res 101:391–404. https://doi.org/10.1016/S0079-6123(08)61965-2
Svennerholm L, Gottfries C-G (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. https://doi.org/10.1046/j.1471-4159.1994.62031039.x
Svennerholm L, Gottfries CG, Blennow K et al (1990) Parenteral administration of GM1 ganglioside to presenile Alzheimer patients. Acta Neurol Scand 81:48–53. https://doi.org/10.1111/j.1600-0404.1990.tb00930.x
Tagami S, Inokuchi JI, Kabayama K et al (2002) Ganglioside GM3 participates in the pathological conditions of insulin resistance. J Biol Chem 277:3085–3092. https://doi.org/10.1074/jbc.M103705200
Tayebi N, Walker J, Stubblefield B et al (2003) Gaucher disease with parkinsonian manifestations: does glucocerebrosidase deficiency contribute to a vulnerability to parkinsonism? Mol Genet Metab 79:104–109. https://doi.org/10.1016/S1096-7192(03)00071-4
Tettamanti G (2004) Ganglioside/glycosphingolipid turnover: new concepts. Glycoconj J 20:301–317
Thudichum JLW (1884) A treatise on the chemical constitution of the brain: based throughout upon original researches. Bailliere, Tindall &, Cox, London.
Todeschini AR, Dos Santos JN, Handa K, Hakomori SI (2007) Ganglioside GM2-tetraspanin CD82 complex inhibits Met and its cross-talk with integrins, providing a basis for control of cell motility through glycosynapse. J Biol Chem 282:8123–8133. https://doi.org/10.1074/jbc.M611407200
Valdes-Gonzalez T, Goto-Inoue N, Hirano W 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
Valsecchi M, Palestini P, Chigorno V, Sonnino S (1996) Age-related changes of the ganglioside long-chain base composition in rat cerebellum. Neurochem Int 28:183–187. https://doi.org/10.1016/0197-0186(95)00069-0
Varki A, Cummings RD, Aebi M et al (2015) Symbol nomenclature for graphical representations of glycans. Glycobiology 25:1323–1324
Walkley SU (2004) Secondary accumulation of gangliosides in lysosomal storage disorders. Semin Cell Dev Biol 15:433–444. https://doi.org/10.1016/j.semcdb.2004.03.002
Walkley SU, Vanier MT (2009) Secondary lipid accumulation in lysosomal disease. Biochim Biophys Acta, Mol Cell Res 1793:726–736
Wang G, Bieberich E (2018) Sphingolipids in neurodegeneration (with focus on ceramide and S1P). Adv Biol Regul 70:51–64
Wang XQ, Sun P, Paller AS (2002) Ganglioside induces caveolin-1 redistribution and interaction with the epidermal growth factor receptor. J Biol Chem 277:47028–47034. https://doi.org/10.1074/jbc.M208257200
Wang RY, Bodamer OA, Watson MS, Wilcox WR (2011) Lysosomal storage diseases: diagnostic confirmation and management of presymptomatic individuals. Genet Med 13:457–484. https://doi.org/10.1097/GIM.0b013e318211a7e1
Watanabe R, Ohyama C, Aoki H et al (2002) Ganglioside G(M3) overexpression induces apoptosis and reduces malignant potential in murine bladder cancer. Cancer Res 62:3850–3854
Wennekes T, Van Den Berg RJBHN, Boot RG et al (2009) Glycosphingolipids – nature, function, and pharmacological modulation. Angew Chemie Int Ed 48:8848–8869
Wertz PW (2018) Naturally occurring ω-hydroxyacids. Int J Cosmet Sci 40:31–33
White AB, Givogri MI, Lopez-Rosas A et al (2009) Psychosine accumulates in membrane microdomains in the brain of Krabbe patients, disrupting the raft architecture. J Neurosci 29:6068–6077. https://doi.org/10.1523/JNEUROSCI.5597-08.2009
Wong K, Sidransky E, Verma A et al (2004) Neuropathology provides clues to the pathophysiology of Gaucher disease. Mol Genet Metab 82:192–207. https://doi.org/10.1016/j.ymgme.2004.04.011
Wu G, Lu ZH, Xie X, Ledeen RW (2004) Susceptibility of cerebellar granule neurons from GM2/GD2 synthase-null mice to apoptosis induced by glutamate excitotoxicity and elevated KCl: Rescue by GM1 and LIGA20. Glycoconj J 21:305–313. https://doi.org/10.1023/B:GLYC.0000046273.68493.f7
Wu G, Lu ZH, Wang J et al (2005) Enhanced susceptibility to kainate-induced seizures, neuronal apoptosis, and death in mice lacking gangliotetraose gangliosides: protection with LIGA 20, a membrane-permeant analog of GM1. J Neurosci 25:11014–11022. https://doi.org/10.1523/JNEUROSCI.3635-05.2005
Wu G, Lu ZH, Kulkarni N, Ledeen RW (2012) Deficiency of ganglioside GM1 correlates with Parkinson’s disease in mice and humans. J Neurosci Res 90:1997–2008. https://doi.org/10.1002/jnr.23090
Yamamoto N, Matsubara T, Sato T, Yanagisawa K (2008) Age-dependent high-density clustering of GM1 ganglioside at presynaptic neuritic terminals promotes amyloid β-protein fibrillogenesis. Biochim Biophys Acta Biomembr 1778:2717–2726. https://doi.org/10.1016/j.bbamem.2008.07.028
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. https://doi.org/10.1073/pnas.0635898100
Yanagisawa M, Ariga T, Yu RK (2010) Cytotoxic effects of GM1 ganglioside and amyloid β-peptide on mouse embryonic neural stem cells. ASN Neuro 2:49–56. https://doi.org/10.1042/AN20090063
Yang R, Wang Q, Min L 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. https://doi.org/10.1007/s10072-012-1263-y
Yates AJ, Rampersaud A (1998) Sphingolipids as receptor modulators: an overview. Ann N Y Acad Sci 845:57–71. https://doi.org/10.1111/j.1749-6632.1998.tb09662.x
Yednak MA, Bremer EG (1994) Preferential binding of the epidermal growth factor receptor to ganglioside GM3 coated plates. Mol Chem Neuropathol 21:369–378. https://doi.org/10.1007/BF02815362
Yo S, Hamamura K, Mishima Y et al (2019) Deficiency of GD3 synthase in mice resulting in the attenuation of bone loss with aging. Int J Mol Sci 20. https://doi.org/10.3390/ijms20112825
Yoon SJ, Nakayama KI, Hikita T et al (2006a) Epidermal growth factor receptor tyrosine kinase is modulated by GM3 interaction with N-linked GlcNAc termini of the receptor. Proc Natl Acad Sci U S A 103:18987–18991. https://doi.org/10.1073/pnas.0609281103
Yoon SJ, Nakayama KI, Takahashi N et al (2006b) Interaction of N-linked glycans, having multivalent GlcNAc termini, with GM3 ganglioside. Glycoconj J 23:639–649. https://doi.org/10.1007/s10719-006-9001-4
Yoshizaki F, Nakayama H, Iwahara C et al (2008) Role of glycosphingolipid-enriched microdomains in innate immunity: microdomain-dependent phagocytic cell functions. Biochim Biophys Acta Gen Subj 1780:383–392
Yuyama K, Sun H, Sakai S et al (2014) Decreased amyloid-β pathologies by intracerebral loading of glycosphingolipid-enriched exosomes in Alzheimer model mice. J Biol Chem 289:24488–24498. https://doi.org/10.1074/jbc.M114.577213
Zesiewicz TA (2019) Parkinson disease. Contin Lifelong Learn Neurol 25:896–918
Zhang X, Kiechle FL (2004) Review: glycosphingolipids in health and disease. Ann Clin Lab Sci 34:3–13
Zhou Q, Hakomori S, Kitamura K, Igarashi Y (1994) GM3 directly inhibits tyrosine phosphorylation and de-N-acetyl-GM3 directly enhances serine phosphorylation of epidermal growth factor receptor, independently of receptor-receptor interaction. J Biol Chem 269:1959–1965
Zhu Y, Yang J, Jiao S, Ji T (2013) Ganglioside-monosialic acid (GM1) prevents oxaliplatin-induced peripheral neurotoxicity in patients with gastrointestinal tumors. World J Surg Oncol 11. https://doi.org/10.1186/1477-7819-11-19
Zunke F, Moise AC, Belur NR, et al (2018) Reversible conformational conversion of α-Synuclein into toxic assemblies by glucosylceramide. Neuron 97:92–107.e10. https://doi.org/10.1016/j.neuron.2017.12.012
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 The Author(s), under exclusive license to Springer Nature Switzerland AG
About this chapter
Cite this chapter
Chiricozzi, E. et al. (2021). Glycosphingolipids. In: Lauc, G., Trbojević-Akmačić, I. (eds) The Role of Glycosylation in Health and Disease. Advances in Experimental Medicine and Biology, vol 1325. Springer, Cham. https://doi.org/10.1007/978-3-030-70115-4_3
Download citation
DOI: https://doi.org/10.1007/978-3-030-70115-4_3
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-70114-7
Online ISBN: 978-3-030-70115-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)