Gangliosides in Axon Stability and Regeneration

Abstract

Gangliosides are a family of sialic acid-containing glycosphingolipids highly expressed in the nervous system of vertebrates. Over the last 25years, research has unmasked several of their neurobiological functions but the role of gangliosides in the nervous system remains not fully elucidated. Genetic disruption of genes for key enzymes involved in ganglioside biosynthesis led to the discovery of their diverse functions and highlighted the exquisite structural specificity required in this processes. In the nervous system, gangliosides regulate axonal caliber and organize ion channels at the nodes of Ranvier, a critical step to ensure fast conduction velocity of myelinated fibers. They also act as receptors for lectins located on apposing myelin membranes critical to maintain axon-glia interactions that result in cytoskeleton stabilization. After a lesion, gangliosides acting as receptors for glial-derived molecules present in the extracellular milieu can halt axon regeneration. Similarly, antiganglioside antibodies present in autoimmune neurological conditions can mimic this inhibitory effect on nerve repair. Studying the molecular details of the molecular interaction of gangliosides in trans with ligands present on apposing cell membranes and receptor/transducer molecules in cis interaction at the axolemma membrane, together with their downstream signaling pathways, represent a unique opportunity to expand our knowledge about the role of gangliosides in the nervous system.