Possible Association of Degenerative Motor Neuron Disease (ALS) with Abnormal Ganglioside Metabolism: Abnormal Gangliosides in ALS Spinal Cord and ALS-Like Symptoms in a Unique Partial HexB Deficiency Syndrome

  • G. Dawson
  • L. W. Hancock
  • A. L. Horwitz
  • R. Wollman
  • N. Cashman
  • J. Antel
Part of the FIDIA Research Series book series (FIDIA, volume 6)


Two major ganglioside storage diseases are known in man, GM2 (II3NeuAcGgOse3Cer)-Gangliosidosis (Tay-Sachs disease and its β-hexosaminidasedeficient variants) and GM1-gangliosidosis (β-Galactosidase deficiency) (O’Brien, 1983). Both diseases encompass many genotypic variants and many clinical phenotypes, but the major pathological characteristic is the lysosomal accumulation of gangliosides in neurons (O’Brien, 1983). Ultrastructural studies of neurons in humans and animals with GM2- and GM1-gangliosidosis have revealed aberrant sprouting of neurites from axon hillocks (meganeurites) (Purpura and Suzuki, 1976) prior to neuronal death and this has led to much of the current interest in gangliosides as neuritogenic agents. Much of this Symposium will be devoted to the stimulatory, neurite regenerative capacity of gangliosides, so it is important to remember the neuropathological origins of the “ganglioside effect”.


Amyotrophic Lateral Sclerosis Spinal Muscular Atrophy Motor Neuron Disease Sandhoff Disease Rectal Suction Biopsy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



amyotrophic lateral sclerosis


sodium dodecylsulphate


electron microscopy

4MU (4MU-)

4 methyl umbelliferone (4-methylumbelliferyl-)


platelet derived growth factor


epithelial cells growth factor


polyacrylamide gel electrophoresis


thin layer chromatography.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Argov Z, Navon R (1984) Clinical and genetic variations in the syndrome of adult GM2 gangliosidosis resulting from hexosaminidase A deficiency. Ann Neurol 16: 14–20.PubMedCrossRefGoogle Scholar
  2. Berry-Kravis L, Dawson G (1984) Gangliosides as modulators of the coupling of neurotransmitters to adenylate cyclase. In: Ledeen RW, Yu RK, Rapport MM, Suzuki K (eds): Ganglioside Structure, Function and Biomedical Potential. Plenum press, New York, pp. 341–353.Google Scholar
  3. Brady RO, Fishman P (1974) Biosynthesis of glycolipids in virus-transformed cells. Biochim Biophys Acta 335: 121–148.Google Scholar
  4. Cashman NR, Antel JP, Hancock LW, Dawson G, Horwitz AL, Johnson WG, Huttenlocher PR, Wollmann RL (1985) Ann Neurol 19: 568–572.CrossRefGoogle Scholar
  5. Cuatrecasas P (1973) Interaction of vibrio cholerae enterotoxin with cell membranes. Biochemistry 12: 3547–3582.PubMedCrossRefGoogle Scholar
  6. Dawson G, Stefansson K (1984) Gangliosides of human spinal cord: Aberrant composition of cords from patients with amyotrophic lateral sclerosis. J Neurosci Res 12: 213–220. Dawson G, Tsay G (1977) Substrate specificity of human a-L-fucosidase. Arch Biochem Biophys 184: 12–23.Google Scholar
  7. Dodd J, Solter D, Jessel T (1984) Monoclonal antibodies against carbohydrate differentiated antigens identify subsets of primary sensory neurones. Nature 311: 469–472.PubMedCrossRefGoogle Scholar
  8. Fox MF, Dutoit DL, Warnich L, Retief AE (1984) Regional localization of a-galactosidase (GAL) to Xpter -’ q22, hexosaminidase B (HexB) to 5q13 qter and arylsulfatase B (ARSB) to 5 pter q13. Cytogenet Cell Genet 38: 45–49.PubMedCrossRefGoogle Scholar
  9. Frisch A, Baram D, Navon R (1984) Hexosaminidase A deficiency adults: presence of a-chain precursor in cultured skin fibroblasts. Biochem Biophys Res Commun. 119: 101–107.PubMedCrossRefGoogle Scholar
  10. Hancock LW, Horwitz AL, Cashman NR, Antel JP, Dawson G (1985) N-acetyl-ßhexosaminidase deficiency in cultured fibroblasts from a patient with progressive motor disease. Biochem Biophys Res Commun 130: 1185–1192.PubMedCrossRefGoogle Scholar
  11. Hancock L, Li YT, Dawson GD (1985) Abnormal glycolipid metabolism in a patient with HexB deficiency. J Biol Chem, in press.Google Scholar
  12. Hasilik A and Neufeld EF (1980) Biosynthesis of lysosomal enzymes in fibroblasts synthesis as precursors of higher molecular weight. J Biol Chem 255: 4937–4945.PubMedGoogle Scholar
  13. Johnson W (1981) The clinical spectrum of hexosaminidase deficiency diseases. Neurology 31: 1453–1456.PubMedCrossRefGoogle Scholar
  14. Johnson WG, Wigger HJ, Karp HR (1982) Juvenile spinal muscular atrophy: °A new hexosaminidase phenotype. Ann Neurol 11: 11–16.PubMedCrossRefGoogle Scholar
  15. Kolodny EH, Raghavan SS (1983) GM2-Gangliosidosis. Trends in Neurol Sci 6: 16–20. Kundu SK, Harati Y, Misra LK (1984) Sialosylglobotetraoscylceramide: A marker for amyotrophic lateral sclerosis. Biochem Biophys Res Commun 118: 82–89.Google Scholar
  16. Ledeen RW (1985) Gangliosides of the neuron. Trends in Neurol Sci 9: 169–174.CrossRefGoogle Scholar
  17. Mitsumoto H, Sliman RJ, Schafer IA, Sternick CS, Kaufman B, Wilbourn A, Horwitz SJ (1985)Google Scholar
  18. Motor neuron disease and adult hexosaminidase A deficiency in two families: Evidence forGoogle Scholar
  19. multisystem degeneration. Ann Neurol 17: 378–385.Google Scholar
  20. Myerowitz R, Robins AR, Proia RL, Sahagian GG, Puchalski CM and Neufeld EF (1983) Nacetyl-ß-D-hexosaminidase. Method Enzymol 96: 729–736.Google Scholar
  21. O’Brien JS (1983) Gangliosides. In: Stanbury JB, Wyngaarden JB, Fredrickson DS, Goldstein JL, Brown MS (eds): The Metabolic Basis of Inherited Disease. McGraw-Hill, New York, pp. 945–969.Google Scholar
  22. O’Dowd B, Quan F, Willard HF, Lamhonwah AM, Korneluk RG, Lowden JA, Gravel RA, Mahuren DJ (1985) Isolation of cDNA clones encoding the 0-hexosaminidase gene. Proc Natl Acad Sci USA 82: 1184–1188.PubMedCrossRefGoogle Scholar
  23. Purpura DP, Suzuki K (1976) Distortion of neuronal geometry and formation of aberrant synapses in neuronal storage diseases. Brain Res 116: 1–21.PubMedCrossRefGoogle Scholar
  24. Rapport MM, Donnenfeld H, Brunner W, Hungund B, Bartfeld H (1985) Ganglioside patterns in amyotrophic lateral sclerosis brain regions. Neurology, in press.Google Scholar
  25. Yamakawa T, Nagai Y (1978) Biological role of glycolipids. Trends Biochem Sci 3: 128–131.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1986

Authors and Affiliations

  • G. Dawson
    • 1
  • L. W. Hancock
    • 1
  • A. L. Horwitz
    • 1
  • R. Wollman
    • 1
  • N. Cashman
    • 1
  • J. Antel
    • 1
  1. 1.Joseph P. Kennedy Jr. Mental Retardation Research Center, Departments of Pediatrtics, Neurology and PathologyUniversity of ChicagoChicagoUSA

Personalised recommendations