Gangliosides turnover and neural cells function: A new perspective

There is a possibility that ganglioside turnover plays a major role in the formation of intracellular metabolic regulators. The chapter focuses on the evidence supporting this possibility, with particular reference to neural cells function. Gangliosides are involved in many nerve cell functions and the concept of a multifunctional role for these molecules seems the most flexible and suitable way to explain different functional behaviors. This wider view of interpreting ganglioside function includes the challenging hypothesis that gangliosides contribute to generate a new family of metabolic second messengers, comprising sphingosine, ceramide, and some of their derivatives. On the basis of the present knowledge, the only conceivable link between ganglioside metabolism and formation of compounds of a sphingoid nature is intra-lysosomal breakdown of membrane-bound gangliosides subsequent to endocytosis. Therefore, the suggestion is that external ligand binding to ganglioside affects the rate of ganglioside endocytosis and/or their sorting from endosomes to lysosomes. Consequently, their metabolic processing and the subsequent formation of second messengers of sphingoid nature turn out to be modified. The final effect is a modulation of cellular responses. The various aspects of this new perspective as well as assessment of its applicability to definite aspects of nerve cell function must be precisely defined and require the development of new experimental designs and ideas.