Sphingolipids and gangliosides of the nervous system in membrane function and dysfunction

Abstract

a b s t r a c tSimple sphingolipids such as ceramide and sphingomyelin (SM) as well as more complex glycosphingolipids play very important roles in cell function under physiological conditions and during disease development and progression. Sphingolipids are particularly abundant in the nervous system. Due to their amphiphilic nature they localize to cellular membranes and many of their roles in health and disease result from membrane reorganization and from lipid interaction with proteins within cellular membranes. In this review we discuss some of the functions of sphingolipids in processes that entail cellular membranes and their role in neurodegenerative diseases, with an emphasis on SM, ceramide and gangliosides.

Ganglioside GM1 induces phosphorylation of mutant huntingtin and restores normal motor behavior in Huntington disease mice

“…GM1 is a lipid with important modulatory roles in the nervous system (18). In HD, decreased levels of this and other gangliosides, as we recently reported (19), are likely to affect cell signaling and neuronal function.…”

“…Recently, we and other groups reported that levels of GM1, a ganglioside involved in cell signaling (18), are decreased in HD models (19)(20)(21), in fibroblasts isolated from HD patients (19), and in postmortem human HD brain samples (20,21). Gangliosides are sialic acid-containing glycosphingolipids highly abundant in the brain, where they exert a plethora of important cell regulatory functions (18).…”

“…Gangliosides are sialic acid-containing glycosphingolipids highly abundant in the brain, where they exert a plethora of important cell regulatory functions (18). They are major components of membrane microdomains known as "lipid rafts" (22) and are important players in cell signaling (23) and cell-cell interaction (24).…”

New Insights into the Regulation of Serine Palmitoyltransferase

“…They are important components of membranes, predominantly found in the plasma membrane in contrast to the intracellular membranes which have less sphingolipids (87). The chemical properties of the sphingolipids modulate the physical properties of membrane bilayers such as insulation and barrier functions of myelin (71) and skin (42). Sphingolipids also affect vesicular transport by influencing membrane curvature.…”

Ganglioside GM1 for ischemic stroke: An update (2005-2015)

“…At that time, gangliosides were a relatively hot topic and the subject of many international meetings. Soon afterwards it was also found to be able to potentiate the action of neurotrophins and display a wide variety of central nervous system (CNS) functions including promoting survival, differentiation [2], neurodegeneration [3][4][5], axon stability, and regeneration [6]. Although the development of the acute inflammatory polyneuropathy Guillain-Barre´ syndrome (GBS) after intravenous ganglioside treatment resulted in the withdrawal of GM1 from the European market [7], this adverse effect was shown to be rare [8].These drugs are still available and have been extensively prescribed in other markets, including in China, where a multitude of neurological maladies are treated with gangliosides in the absence of resultant GBS or other severe adverse events [9][10][11][12].…”