Gangliosides actions

Two of the most widely spread and well-studied enterotoxigenic forms of bacterial diarrhea are ETEC and Vibrio cholerae. The toxins they produce, labile toxin (LT) and cholera toxin (CT) respectively, are very similar in primary sequence, structure, and mechanism of action [72]. They are homologous multi-subunit proteins in which the non-toxic B subunit mediates GMj ganglioside binding, and thus are candidates for vaccines that can neutralize toxin activity. 

The clinical effects of chloroform toxicity on the central nervous system are well documented. However, the molecular mechanism of action is not well understood. It has been postulated that anesthetics induce their action at a cell-membrane level due to lipid solubility. The lipid-disordering effect of chloroform and other anesthetics on membrane lipids was increased by gangliosides (Harris and Groh 1985), which may explain why the outer leaflet of the lipid bilayer of neuronal membranes, which has a large ganglioside content, is unusually sensitive to anesthetic agents. Anesthetics may affect calcium-dependent potassium conductance in the central nervous system (Caldwell and Harris 1985). The blockage of potassium conductance by chloroform and other anesthetics resulted in depolarization of squid axon (Haydon et al. 1988). 

The aeylneuraminic acids can be released from their glycosidic linkages either by dilute (aqueous or methanolie) acids or sialidases. Special care must be taken in the isolation of the rather labile, O-acv-lated sialic acids, which arc partially non-susceptible to the action of sialidases. Furthennore, in gangliosides, non-O-acetylated sialic acid residues occur, and these are also more or less resistant towards these enzymes. 

RNA interference-mediated silencing of GM3 synthase protects HT22 cells from glutamate-mediated cell death. Collective evidence suggests that GM1 and GM3 gangliosides act very differently in brain tissue and more studies are required on the molecular mechanism of action of various gangliosides in brain tissue. 

Figure 12. Time course of NeuAc release from liposome-associated ganglioside Gn,a by the action of Vibrio cholerae sialidase...

Figure 13. Time course of oxidation of the terminal galactose residue of liposome-associated ganglioside G.VI by the action of galactose oxidase...

NEUROTROPHIC AND NEUROPROTECTIVE ACTIONS OF AN ENHANCER OF GANGLIOSIDE BIOSYNTHESIS... 

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