Role of GM3 ganglioside in the pathology of some progressive human diseases and prognostic importance of serum anti-GM3 antibodies

Abstract

Glycosphingolipids (gangliosides) have been characterized as important biological molecules with a key role as regulators in many physiological processes on cellular, tissue, organ, and organism levels. The deviations in their normal amounts, production, and metabolism are very often related to the development of many multi-factor socially important diseases. GM3 ganglioside, as a small molecule, plays important roles in the cascade regulatory pathways in the pathology of many disorders like neurodegenerative diseases, autoimmune diseases, inflammation, diabetes, malignant transformation, and others. Ganglioside GM3 and its derivatives are membrane-bound glycosphingolipids composed of an oligosaccharide head structure containing one sialic acid residue. These molecules transduce signals involved in cell surface events, including the phosphorylation of transmembrane receptors. This ganglioside is the most widely distributed among tissues, and it serves as a precursor for most of the more complex ganglioside species. GM3 inhibits the function of fibroblast growth factor receptor, and cell growth is regulated by GM3-enriched microdomain. GM3 is thought to inhibit immunologic functions, such as the proliferation and production of cytokines by T cells. On the other hand, the anti-ganglioside antibodies (AGAs) are important in many acquired demyelinating immunemediated neuropathies, like Multiple sclerosis (MS), Guillain–Barré syndrome (GBS) and its variation, Miller–Fisher syndrome (MFS) and could be suggested as important diagnostic and prognostic markers about the describe diseases and their etiology. We show that the complexes of anti-ganglioside antibodies to GM3 (detected by ELISA) may be useful diagnostic and prognostic tool markers for autoimmune diseases, neurodegenerative disorders, malignancy, diabetes, and inflammation. Our pilot studies suggest increased serum IgG anti-GM3 antibodies titers in patients with secondary progressive MS (SPMS), throat cancer, elder people with diabetes (89–96 years), old Lewis rats (30–33 months), and in the serum of subjected on lead intoxication BALB/c mice treated by salinomycin. We observed no changes in the titers in healthy elder people (89–96 years), in 70-year-old woman on dialysis, in relapsing-remitting MS (RRMS) patients on long-term treatment with Glatiramer acetate, Laquinimod, and Interferons, as well as in 18– 22 months old Wistar rats and subjected on lead intoxication BALB/c mice treated by monensin and dimercaptosuccinic acid (DMSA). Considerable decrease of serum GM3 in early MS correlate with early damage and severe destruction of the blood–brain barrier, which provides impetus to initiate early therapy.