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
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”.
KeywordsAmyotrophic Lateral Sclerosis Spinal Muscular Atrophy Motor Neuron Disease Sandhoff Disease Rectal Suction Biopsy
amyotrophic lateral sclerosis
- 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.
- 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
- Brady RO, Fishman P (1974) Biosynthesis of glycolipids in virus-transformed cells. Biochim Biophys Acta 335: 121–148.Google Scholar
- 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
- Hancock L, Li YT, Dawson GD (1985) Abnormal glycolipid metabolism in a patient with HexB deficiency. J Biol Chem, in press.Google Scholar
- 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
- Mitsumoto H, Sliman RJ, Schafer IA, Sternick CS, Kaufman B, Wilbourn A, Horwitz SJ (1985)Google Scholar
- Motor neuron disease and adult hexosaminidase A deficiency in two families: Evidence forGoogle Scholar
- multisystem degeneration. Ann Neurol 17: 378–385.Google Scholar
- 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
- 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
- Rapport MM, Donnenfeld H, Brunner W, Hungund B, Bartfeld H (1985) Ganglioside patterns in amyotrophic lateral sclerosis brain regions. Neurology, in press.Google Scholar