Abstract
Acidic glycosphingolipids, i.e., gangliosides, are predominantly and consistently expressed in nervous tissues of vertebrates at high levels. Therefore, they are considered to be involved in the development and function of nervous systems. Recent studies involving genetic engineering of glycosyltransferase genes have revealed novel aspects of the roles of gangliosides in the regulation of nervous tissues. In this review, novel findings regarding ganglioside functions and their modes of action elucidated mainly by studies of gene knockout mice are summarized. In particular, the roles of gangliosides in the regulation of lipid rafts to maintain the integrity of nervous systems are reported with a focus on the roles in the regulation of neuro-inflammation and neurodegeneration via complement systems. In addition, recent advances in studies of congenital neurological disorders due to genetic mutations of ganglioside synthase genes and also in the techniques for the analysis of ganglioside functions are introduced.
Highlights
Nervous tissues are differentiated from the ectoderm, and their morphology is determined before birth
Mechanisms for signal regulation in cancer cells and PC12 cells based on gangliosides expression between GM1 synthase and GD3 synthase on phenotypes of various cancer cell lines have with different numbers of sialic acids remain unclear, it could be a reflection of regulatory functions been observed [19,20]
We reported the involvement of complement systems in neuro-inflammation as a novel aspect of ganglioside deficiency [80]
Summary
Nervous tissues are differentiated from the ectoderm, and their morphology is determined before birth. PC12 contrastive effects of gene expression between GM1 synthase and GD3 synthase on phenotypes of cells overexpressing GM1 showed reduced sensitivity to the nerve growth factor (NGF), leading to various cancer cell lines have been observed [19,20] From these results, it has been demonstrated that lowered neurite extension, and exhibited suppressed activation of TrkA/Ras/ERK1/2 signals upon NGF monosialylgangliosides and disialylgangliosides play distinct roles in the regulation of malignant stimulation [17]. Mechanisms for signal regulation in cancer cells and PC12 cells based on gangliosides expression between GM1 synthase and GD3 synthase on phenotypes of various cancer cell lines have with different numbers of sialic acids remain unclear, it could be a reflection of regulatory functions been observed [19,20] From these results, it has been demonstrated that monosialylgangliosides and of gangliosides in organogenesis and differentiation of nervous tissues and cells. Various changes in ganglioside composition under physiological and pathological conditions have been investigated [2,8,22]
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