Pathological roles of ganglioside mimicry in guillain-barré syndrome and related neuropathies

Gangliosides, sialic acid-containing glycosphingolipids (GSLs), are a family of diverse, highly complex molecules localized primarily on the plasma membrane and particularly abundant in the nervous tissues of vertebrates. Research interest in gangliosides is not limited to their normal biological functions, such as neurotrophicity, cell-cell recognition and adhesion, cellular differentiation and growth, intercellular signaling, and trafficking and/or sorting [17, 19, 61, 62], or on the important constituents of cell surface microdomains or lipid rafts [18, 25, 44]. Research is also focused on the role of gangliosides in the pathogenic mechanisms of many immune-mediated neurological disorders, such as Guillain-Barré syndrome (GBS) [5, 57, 63]. For the putative pathogenic roles of gangliosides, accumulating evidence indicates that (a) gangliosides are localized in peripheral nerve system (PNS) myelin and axolemma, and degeneration of myelin and axons accounts for the loss of sensory and motor functions; (b) animal models of peripheral neuropathies can be established using certain pure gangliosides as the immunogens; and (c) the pathophysiological effects of the antibodies could be due to one or more of the following mechanisms: an antibody-mediated, complement-dependent process; a cell-mediated degenerating process; and a conduction block at the node of Ranvier.