Gangliosides are glycolipids composed of the sphingolipid ceramide and an oligosaccharide with one or more sialic acid (N-acetylneuraminic acid; NANA) residues, which give them a net negative charge. They reside in the outer plasma membrane of animal cells and some intracellular membranes. They are the major constituents of neuronal cell membranes and endoplasmic reticulum. Gangliosides may have a variety of functions in cells. They are thought to provide protection from harsh conditions, such as low pH and degradative enzymes, in the extracellular environment. They can help cells interact with extracellular matrices and other cells and serve as surface receptors for bacterial toxins and, perhaps, normal, endogenous extracellular molecules. Also, these complex glycolipids have an influence on the electrical field across the cellular membrane, as well as the concentration of ions on the external surface of the cells. In addition, gangliosides may have a role in electrical insulation in myelin cells in the nervous system. Some gangliosides are useful as cancer cell markers, since they are elevated in the membranes of certain types of tumor cells, such as melanomas and metastatic brain tumors. Purified gangliosides are frequently used as standards in TLC analysis of cell membranes and as markers for characterization of various cell types. They may also serve as substrates and inhibitors of glycosidases and glycosyl transferases. In addition, gangliosides can insert into cell membranes to alter cellular membrane binding capacity for bacterial toxins, growth factors and hormones. Pretreatment with gangliosides has been found to protect primary neuronal cell cultures from glutamate and kainate neurotoxicity. Also, metabolites of some gangliosides are active as potent and reversible inhibitors of protein kinase C. Due to their importance in nerve cells, another use of gangliosides has been as antigens to produce anti-ganglioside antibodies for neurobiologic investigations. Such antibodies have been injected into animals to generate models for studies of epilepsy and other neurological disorders. References: 1. For classification of gangliosides see Svennerholm, L., et al. (eds.), Structure and Function of Gangliosides, New York, Plenum, 1980. investigations.