Gangliosides ganglioside desialylation

Ganglioside desialylation would reduce the density of negative charges on the presynaptic membranes, thereby preventing the sticking of cationic neurotransmitters, which would in... 

The neuraminidases together with gangliosides have been localized in the nerve ending structures (6, 7 ). Theoretically the sialylation and desialylation cycle may mediate a cyclic reaction at a very important locale in a nerve synaptic structure. This hypothetical involvement of sialic acid metabolism in synaptic transmission has gained support from several studies which have suggested a synaptic localization of the glycosyltransferases (8, 9,10,11) and from proposed theoretical models in which the sialo-glycolipids are considered an important constituent in the functional units of neuronal membranes (12,13,14). 

FIGURE 5.18 Desialylation/sialylation cycle in the presynaptic membrane. Upon release from synaptic vesicles, cationic neurotransmitters (monoamines) would be glued by the negatively charged polysialylated gangliosides of the presynaptic membrane. To avoid this problem, it has been suggested that those gangliosides may be transiently desialylated by neuraminidase (sialidase), and then resialylated by sialytransferase (sialyl-Tf). The concentration of both enzymes in synaptosomes is consistent with such a scenario. 

Gangliosides can stimulate pig ileum and rabbit duodenum (Bogoch et al. 1962, Kirschner and Vogt 1961), while desialylation leads to a loss of this biological activity. Similarly, desialylated gangliosides block the respiration of brain mitochondria (Mkheyan and Sotskii 1970), but it is worth mentioning that part of sialic acid is resistant to neuraminidase treatment (Schauer et al. 1980). 

In addition to these methods, new techniques based on the principle of enzyme-linked immunosorbent assay (ELISA) have recently been introduced for sialidase assay. A glycoprotein or ganglioside substrate is coated in plastic microtiter wells and incubated with an enzyme preparation, followed by detection of the desialylated product using an appropriate ligand. Thus, the activity of Clos-... 

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