Gangliosides in molecular interactions and cell regulation.

Gangliosides are sialoglycolipids expressed by all vertebrate cells. They are found predominantly on the outer leaflet of the plasma membrane but also on select intracellular membranes. As sphingolipids they dynamically associate into lipid rafts where they modulate the activity of receptors and ion channels and serve as ligands for sialoglycan binding proteins on other cells or in the extracellular milieu. Gangliosides support nervous system stability, regulate neurotransmitter and ion channel expression and activity, regulate receptor protein kinases, are responsible for select binding of toxins and pathogens, and have other molecular/cellular regulatory functions. Rare subjects with congenital disorders of ganglioside biosynthesis suffer severe and broad multi-system deficits. Changes in ganglioside expression are characteristic of cancer and neurodegenerative diseases, leading to targeting or use of gangliosides therapeutically. This review presents properties of gangliosides, mechanisms and examples of their physiological and pathological functions, and examples of their roles in human diseases.