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Glycobiology of gangliosides (a family of sialic acid-containing glycosphingolipids) is rapidly expanding for the past five years, focusing on the functional and molecular biological aspects. Two contrasted trends arise in the studies of bioactive gangliosides in terms of biosignaling mechanism. Many glycosyltransferases were now cloned and progress in molecular genetic approaches using these clones present new enigmas concerning glycolipid functions. Gangliosides, a family of sialic acid-containing glycosphingolipids, were first discovered by E. Klenk in 1935 in the brain of a patient with an inherited metabolic disorder (infantile amaurotic idiocy) called Tay- Sachs disease. The disease is known to be one of the lysosomal diseases, which is deficient in a catabolic enzyme of gangliosides, B- 1,4-N-acetylgalactosaminidase, resulting in the accumulation of GM2 gangliosides (Fig. 1 and 2). Tay-Sachs ganglioside GM2 opened a path to the studies of gangliosides as well as sialic acids and related compounds. Brain tissues are uniquely rich in a particular family of gangliosides different from those in extraneural tissues. The brain gangliosides are characterized principally by having N-acetylgalactosamine as a constituent, while the latter by N-acetylglucosamine. The first extraneural ganglioside, Gh43, was isolated from equine erythrocytes by T. Yamakawa in 195 1. Up to the present, the number of gangliosides so far determined in vertebrates is around 126 and the number of brain gangliosides is presumed to be more than forty, most of which represent minor components (Fig. 3) (ref. 1). As seen in other glycosphingolipids extraneural gangliosides of vertebrates show distinct variation in molecular species according to animal species, organ, tissue and cell types. In other words, they may constitute cell surface markers or the face of cells. In contrast, molecular species of brain gangliosides are relatively conserved. GM1 GalPl-3GalNAcPl-4 GalP1-4GlcP1-1 ceramide h$mlNZ: SM3 NeuAc N uAc GQ1

Ganglioside research: New trends and reflections