Stereochemistry of Sphingolipids in Ganglioside GM3 Enhances Recovery of Nervous Functionality

GM3 is a simple monosialylated ganglioside (NeuAc & alpha;(2-3)-Gal & beta;(1-4)-Glc & beta;1-1 & PRIME;-ceramide).Its aberrant expression in adipocytes is involved in a variety ofphysiological and pathological processes in diabetes mellitus andobesity. GM3 is exposed on the outer surface of cell membranes andis strongly associated with type 2 diabetes and insulin resistance.Exogenously added GM3 promotes neurite outgrowth in a variety of differentneuroblastoma cell lines. Neurite outgrowth is a key process in thedevelopment of functional neuronal circuits and neuro-regenerationfollowing nerve injury. Therefore, regulating GM3 levels in nervetissues might be a potential treatment method for these disorders.Here, we demonstrate the comprehensive synthesis of stereoisomericGM3s and compare their physicochemical properties with those of naturalGM3 and diastereomers of sphingolipids in GM3 to examine the enhancementof biological activity. l-erythro-GM3 wasconfirmed to increase neurite outgrowth, providing valuable insightsfor potential neuro-regenerative treatments.

Automated summary

GM3, a monosialylated ganglioside, is involved in various physiological and pathological processes in diabetes and obesity. Its aberrant expression in adipocytes is strongly associated with type 2 diabetes and insulin resistance. Exogenous GM3 can promote neurite outgrowth in different neuroblastoma cell lines, suggesting its potential as a treatment for neuro-regeneration.