An attempt will be made to elucidate the mechanisms which regulate the metabolism of glycosphingolipids, and their related glycoproteins, in the central nervous tissue. Particular emphasis will be placed on lysomal hydrolases since deficiencies of these enzymes are directly associated with inherited mental retardation syndromes. Preliminary evidence suggests that the deoxy-sugar L-fucose plays an important role in cell surface phenomena (antigenicity, aggregation, secretion) and the regulation of fucose metabolism in cultured human fibroblasts and mouse neuroblastoma cell lines will be investigated. A variety of neurotumors and their derived clonal cell lines will be examined in order to evaluate the glycosphingolipid specificity of the major neural cell types (neurons, astrocytes and oligodendrocytes. Particular emphasis will be placed on the biological role of sulfatides and gangliosides (sialo-glycolipids) in the central nervous system. Possible approaches to therapy in this group of inherited mental retardation syndromes will be evaluated at the genetic and enzymatic levels. BIBLIOGRAPHIC REFERENCES: Dawson, G., and A.C. Stoolmiller, Comparison of the Ganglioside Composition of Established Mouse Neuroblastoma Cell Strains Grown In Vivo and in Tissue Culture. J. Neurochem. 26, 150 (1976). Dawson, Glyn, and Nicholas J. Lenn. Polysaccharide Metabolism. In: "Handbook of Clinical Neurology" (H.L. Klawans, ed.) Vol. 27, North Holland Publishing Co., Amsterdam, the Netherlands, 1976. Ch. 406.