The role(s) of gangliosides in neural differentiation and repair: a perspective

Gangliosides, sialylated glycosphingolipids, are found in greatest concentration in the brain. While they were first characterized as a unique class of lipids almost 50 years ago, little is known regarding their actual function. It is known that (a) ganglioside composition changes during development, (b) different types of neural cells have specific gangliosides associated with them, (c) the accumulation of gangliosides in certain inborn errors of metabolism results in the formation of aberrant meganeurites, and (d) gangliosides appear to enhance recovery from certain neural traumas. Recent work suggests that it is the oligosaccharide portion of the ganglioside that carries much of the biological specificity. Coupled with observations that ganglioside-binding proteins are present on the plasma membranes of cells, it suggests the hypothesis that gangliosides present on the surface of one cell may interact with specific ganglioside-binding proteins, "receptors," on target cells. As a result of the ganglioside-binding protein interaction, a signal could be transmitted to the cell. This might occur via modulation of the effect of the endogenous ganglioside on the activity of a kinase(s) or by an alteration in ionic flux. The signal would initiate the appropriate cellular response.