Abstract
Gangliosides, sialylated glycosphingolipids, are major glycans on the surfaces of vertebrate nerve cells. All mammals express the same four major brain gangliosides, GM1, GD1a, GD1b, and GT1b, which together comprise 94 % of brain gangliosides in mice and men alike. Among their functions, brain gangliosides GD1a and GT1b on neuronal axons are complementary binding partners for myelin-associated glycoprotein (MAG), which functions in axon-myelin stability and the control of axon regeneration. Human congenital disorders of ganglioside biosynthesis and related mouse genetic models reveal that complex gangliosides are required for long-term axon survival; loss of gangliosides results in paraplegia in humans and similar progressive motor neuropathy in mice. In addition to stabilizing axons, axon-myelin interactions restrict axon regeneration after injury in adults. MAG on residual myelin that persists at sites of central nervous system injury contributes to axon outgrowth inhibition by binding to gangliosides, thereby signaling axons to halt outgrowth. Modulating ganglioside structures on living nerve cells in vitro and in animal models attenuates inhibition and enhances anatomical and motor behavioral outcomes after axonal injury. Knowledge of ganglioside functions in the brain contributes to a more complete understanding of glycosciences in axon-related physiology and pathology.
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
Boccuto L, Aoki K, Flanagan-Steet H, Chen CF, Fan X, Bartel F, Petukh M, Pittman A, Saul R, Chaubey A, Alexov E, Tiemeyer M, Steet R, Schwartz CE (2014) A mutation in a ganglioside biosynthetic enzyme, ST3GAL5, results in salt & pepper syndrome, a neurocutaneous disorder with altered glycolipid and glycoprotein glycosylation. Hum Mol Genet 23:418–433
Boukhris A, Schule R, Loureiro JL, Lourenco CM, Mundwiller E, Gonzalez MA, Charles P, Gauthier J, Rekik I, Costa Lebrigio RF, Gaussen M, Speziani F, Ferbert A, Feki I, Caballero-Oteyza A, Onne-Laporte A, Amri M, Noreau A, Forlani S, Cruz VT, Mochel F, Coutinho P, Dion P, Mhiri C, Schols L, Pouget J, Darios F, Rouleau GA, Marques W Jr, Brice A, Durr A, Zuchner S, Stevanin G (2013) Alteration of ganglioside biosynthesis responsible for complex hereditary spastic paraplegia. Am J Hum Genet 93:118–123
Harlalka G, Lehman A, Chioza B, Baple E, Maroofian R, Cross H, Sreekantan-Nair A, Priestman D, Al-Turki S, McEntagart M, Proukakis C, Royle L, Kozak R, Laila B, Patton M, Wagner K, Coblentz R, Price J, Mezei M, Schlade-Bartusiak K, Platt F, Hurles M, Crosby A (2013) Mutations in B4GALNT1 (GM2 Synthase) underlie a new disorder of ganglioside biosynthesis. Brain 136:3618–3624
Mehta NR, Lopez PH, Vyas AA, Schnaar RL (2007) Gangliosides and Nogo receptors independently mediate myelin-associated glycoprotein inhibition of neurite outgrowth in different nerve cells. J Biol Chem 282:27875–27886
Mountney A, Zahner MR, Lorenzini I, Oudega M, Schramm LP, Schnaar RL (2010) Sialidase enhances recovery from spinal cord contusion injury. Proc Natl Acad Sci USA 107:11561–11566
Pan B, Fromholt SE, Hess EJ, Crawford TO, Griffin JW, Sheikh KA, Schnaar RL (2005) Myelin-associated glycoprotein and complementary axonal ligands, gangliosides, mediate axon stability in the CNS and PNS: neuropathology and behavioral deficits in single- and double-null mice. Exp Neurol 195:208–217
Schnaar RL (2007) Neural functions of glycolipids. In: Kamerling JP, Boons GJ, Lee YC, Suzuki A, Taniguchi N, Voragen AGJ (eds) Comprehensive glycoscience. volume 4: Cell glycobiology and development, health and disease in glycomedicine. Elsevier Science, Amsterdam, pp 323–337
Schnaar RL, Lopez PH (2009) Myelin-associated glycoprotein and its axonal receptors. J Neurosci Res 87:3267–3276
Schnaar RL, Gerardy-Schahn R, Hildebrandt H (2014) Sialic acids in the brain: gangliosides and polysialic acid in nervous system development, stability, disease and regeneration. Physiol Rev 94:461–518
Simpson MA, Cross H, Gurtz K, Priestman DA, Neville DCA, Reinkensmeier G, Wiznitzer M, Proukakis C, Verganelaki A, Pryde A, Patton MA, Dwek RA, Butters TD, Platt FM, Crosby AH (2004) Infantile onset symptomatic epilepsy syndrome caused by homozygous loss of function mutations in GM3 synthase. Nat Genet 36:1225–1229
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer Japan
About this entry
Cite this entry
Schnaar, R.L. (2015). Gangliosides in Axon Stability and Regeneration. In: Taniguchi, N., Endo, T., Hart, G., Seeberger, P., Wong, CH. (eds) Glycoscience: Biology and Medicine. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54841-6_119
Download citation
DOI: https://doi.org/10.1007/978-4-431-54841-6_119
Received:
Accepted:
Published:
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-54840-9
Online ISBN: 978-4-431-54841-6
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences