Glycans are among the most complex biological molecules found in nature, being composed of monosaccharide units in various combinations and linkages, and featuring diverse and asymmetric types of branching. Until the 1970s, glycan structures were generally represented in scientific publications as chemically accurate drawings, or using standard IUPAC-approved abbreviations (Sharon 1986; McNaught 1997; Chester 1998). However, given the complexity of many glycan structures, it became difficult to represent such molecules in publication figures, especially those involving multistep biosynthetic pathways or multiple structures. Thus, various investigators began to use symbols to represent monosaccharides in glycans. In 1978, Kornfeld and colleagues put forward an elegant and simple system for representation of vertebrate glycans (Kornfeld et al. 1978), and it entered into popular use over the next two decades. This system was eventually adopted and standardized by the editors of the first edition of the textbook Essentials of Glycobiology (Varki et al. 1999). While this adoption increased the popularity of the symbols, the system had some limitations and inconsistencies and did not take advantage of color. Anticipating a revision, the editors developed an updated symbol nomenclature, which was made available to the community in 2005 before the publication of the Second Edition (Varki, Cummings, Esko, Freeze, Stanley, Bertozzi, et al. 2009). This nomenclature was adopted and widely disseminated, especially by the NIGMS-funded Consortium for Functional Glycomics (CFG), which also consulted the scientific community on this issue, thus enhancing acceptance. The official version of the Second Edition nomenclature has since been available in the online version of the textbook. A suggested extended version was then presented at the website Glycopedia. Meanwhile, alternate symbol nomenclature systems have been proposed (Harvey et al. 2009). Issues regarding nomenclature tend to be more controversial than the underlying science (Varki, Cummings, Esko, Freeze, Stanley, Marth, et al. 2009), as there is never one correct answer, and some aspects are matters of taste. For example, the two systems mentioned each have some relative advantages and disadvantages.

Every cell in nature carries a rich surface coat of glycans, its glycocalyx, which constitutes the cell's interface with its environment. In eukaryotes, the glycocalyx is composed of glycolipids, glycoproteins, and proteoglycans, the compositions of which vary among different tissues and cell types. Many of the linear and branched glycans on cell surface glycoproteins and glycolipids of vertebrates are terminated with sialic acids, nine-carbon sugars with a carboxylic acid, a glycerol side-chain, and an N-acyl group that, along with their display at the outmost end of cell surface glycans, provide for varied molecular interactions. Among their functions, sialic acids regulate cell-cell interactions, modulate the activities of their glycoprotein and glycolipid scaffolds as well as other cell surface molecules, and are receptors for pathogens and toxins. In the brain, two families of sialoglycans are of particular interest: gangliosides and polysialic acid. Gangliosides, sialylated glycosphingolipids, are the most abundant sialoglycans of nerve cells. Mouse genetic studies and human disorders of ganglioside metabolism implicate gangliosides in axon-myelin interactions, axon stability, axon regeneration, and the modulation of nerve cell excitability. Polysialic acid is a unique homopolymer that reaches >90 sialic acid residues attached to select glycoproteins, especially the neural cell adhesion molecule in the brain. Molecular, cellular, and genetic studies implicate polysialic acid in the control of cell-cell and cell-matrix interactions, intermolecular interactions at cell surfaces, and interactions with other molecules in the cellular environment. Polysialic acid is essential for appropriate brain development, and polymorphisms in the human genes responsible for polysialic acid biosynthesis are associated with psychiatric disorders including schizophrenia, autism, and bipolar disorder. Polysialic acid also appears to play a role in adult brain plasticity, including regeneration. Together, vertebrate brain sialoglycans are key regulatory components that contribute to proper development, maintenance, and health of the nervous system.

Gangliosides are a family of sialic acid-containing glycosphingolipids highly enriched in the mammalian nervous system. Although they are the major sialoglycoconjugates in the brain, their neurobiological functions remain poorly defined. By disrupting the gene for a key enzyme in complex ganglioside biosynthesis (GM2/GD2 synthase; EC 2.4.1.92 ) we generated mice that express only simple gangliosides (GM3/GD3) and examined their central and peripheral nervous systems. The complex ganglioside knockout mice display decreased central myelination, axonal degeneration in both the central and peripheral nervous systems, and demyelination in peripheral nerves. The pathological features of their nervous system closely resemble those reported in mice with a disrupted gene for myelin-associated glycoprotein (MAG), a myelin receptor that binds to complex brain gangliosides in vitro . Furthermore, GM2/GD2 synthase knockout mice have reduced MAG expression in the central nervous system. These results indicate that complex gangliosides function in central myelination and maintaining the integrity of axons and myelin. They also support the theory that complex gangliosides are endogenous ligands for MAG. The data extend and clarify prior observations on a similar mouse model, which reported only subtle conduction defects in their nervous system [Takamiya, K., Yamamoto, A., Furukawa, K., Yamashiro, S., Shin, M., Okada, M., Fukumoto, S., Haraguchi, M., Takeda, N., Fujimura, K., et al. (1996) Proc. Natl. Acad. Sci. USA 93, 10662–10667].