Elucidation of Pathological Mechanisms for Involvement of Gangliosides in Intractable Diseases

Abstract

Acidic glycosphingolipids, gangliosides are mainly expressed in nervous tissues and cancer cells, and regulate the health of the tissues. We generated mutant mice lacking various gangliosides by knocking out ganglioside synthase genes, and reported that these knockout (KO) mice exhibited various neurodegeneration. As one of roles of gangliosides, it was demonstrated that abnormal construction of lipid rafts due to ganglioside deficiency induced chronic inflammation and neurodegeneration in these KO mice. On the other hand, gangliosides expressed in melanomas and gliomas caused shifts of localization of various molecules into lipid rafts. And shift of molecules into lipid rafts enhanced signals, leading to malignant phenotypes. In this review, we reported how gangliosides play a role in maintaining the integrity of neural tissues and regulating cancer properties, based on our findings.