Gangliosides in the Nervous System: Biosynthesis and Degradation

Yu, Robert K.; Ariga, Toshio; Yanagisawa, Makoto; Zeng, Guichao

doi:10.1007/978-3-540-30429-6_41

Cited by 14 publications

(13 citation statements)

References 159 publications

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“…The change in pattern of ganglioside expression in the developing brain has been largely attributed to the temporal regulation of enzymes responsible for their synthesis, namely ganglioside synthases (Yu et al . ). Earlier work suggested that reduced neuraminidase activity was responsible for the elevations of at least some of the simple gangliosides in HS (Walkley ), but more recently a combined effect of ganglioside synthesis and degradation has been implicated.…”

Section: Discussionmentioning

confidence: 97%

Subregional brain distribution of simple and complex glycosphingolipids in the mucopolysaccharidosis type I (Hurler syndrome) mouse: impact of diet

Saville

Thai

Lehmann

et al. 2017

Journal of Neurochemistry

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Gangliosides are the most complex oligosaccharide-containing glycosphingolipids defined by the presence of sialic acid and although present in all tissues, predominate in the brain. Considering their importance in neural development, it is unsurprising that ganglioside metabolism is altered in neurodegenerative diseases. The severe form of mucopolysaccharidosis type I, Hurler syndrome (HS), is characterised by progressive loss of neuronal function through largely undefined mechanisms. Here, we sought to interrogate brain gangliosides in a murine model of HS and further, assessed whether dietary modulation of lipid metabolism effected correction of the metabolic abnormalities. The simple gangliosides, G M2 , G M3 , G D2 and G D3 were elevated in the five subregions examined -brain stem, cerebellum, cortex, hippocampus, subcortex -in HS mice as early as 2 months of age compared with their wild type counterparts. Their elevation persisted at 6 months of age, imparting protracted neurological development as these simple gangliosides have usually subsided by this stage of brain development. Their immediate synthetic precursor, lactosylceramide, was also elevated, suggesting that their increase arises at this metabolic intermediary, as dihydroceramide, ceramide and monohexosylceramide were unaffected. Dietary linoleic acid supplementation significantly reduced G M2 and G M3 , and furthermore, improved exploratory behaviour as assessed by the open field test, highlighting the possibility of further exploring dietary intervention as a therapeutic consideration. Keywords: gangliosides, inborn error of metabolism, linoleic acid, mouse model, neurological disease, tandem mass spectrometry.

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Section: Discussionmentioning

confidence: 97%

Subregional brain distribution of simple and complex glycosphingolipids in the mucopolysaccharidosis type I (Hurler syndrome) mouse: impact of diet

Saville

Thai

Lehmann

et al. 2017

Journal of Neurochemistry

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“…As the brain develops, the expression of these simple gangliosides is down-regulated with concomitant up-regulation of complex gangliosides such as GM1, GD1a, GD1b and GT1b. This change in expression levels and patterns of gangliosides can be largely attributed to the developmental change of the expression levels and patterns of ganglioside synthases (glycosyltransferases) 6,7) that are spatiotemporally regulated, both at the transcriptional and post-translational levels, by multiple systems, including transcription factors 7) and probably epigenetic modifications 8) .…”

Section: Structures and Metabolism Of Gangliosidesmentioning

confidence: 99%

Structures, Biosynthesis, and Functions of Gangliosides-an Overview

Yu¹,

Tsai²,

Ariga³

et al. 2011

J. Oleo Sci.

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329

294

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Gangliosides are sialic acid-containing glycosphingolipids that are most abundant in the nervous system. Heterogeneity and diversity of the structures in their carbohydrate chains are characteristic hallmarks of these lipids; so far, 188 gangliosides with different carbohydrate structures have been identified in vertebrates. The molecular structural complexity increases manifold if one considers heterogeneity in the lipophilic components. The expression levels and patterns of brain gangliosides are known to change drastically during development. In cells, gangliosides are primarily, but not exclusively, localized in the outer leaflets of plasma membranes and are integral components of cell surface microdomains with sphingomyelin and cholesterol from which they participate in cell-cell recognition, adhesion, and signal transduction. In this brief review, we discuss the structures, metabolism and functions of gangliosides.

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“…As the brain develops, the expression of these simple gangliosides is down-regulated with concomitant up-regulation of complex gangliosides such as GM1, GD1a, GD1b and GT1b. This change in expression levels and patterns of gangliosides can be largely attributed to developmental changes of the expression levels and patterns of ganglioside synthases [12, 13] that are spatiotemporally regulated, both at the transcriptional and post-translational levels, by multiple systems including epigenetic modifications [14, 15]. Some of the key GTs whose genes have been cloned and their promoters are functionally analyzed are presented below.…”

Section: Introductionmentioning

confidence: 99%

Functional Roles of Gangliosides in Neurodevelopment: An Overview of Recent Advances

2012

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Summary Gangliosides are sialic acid-containing glycosphingolipids (GSLs) that are most abundant in the nervous system. They are localized primarily in the outer leaflets of plasma membranes and participated in cell-cell recognition, adhesion, and signal transduction and are integral components of cell surface microdomains or lipid rafts along with proteins, sphingomyelin and cholesterol. Ganglioside-rich lipid rafts play an important role in signaling events affecting neural development and the pathogenesis of certain diseases. Disruption of ganglioside synthase genes in mice induces developmental defects and neural degeneration. Targeting ganglioside metabolism may represent a novel therapeutic strategy for intervention in certain diseases. In this review, we focus on recent advances on metabolic and functional studies of gangliosides in normal brain development and in certain neurological disorders.

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Gangliosides in the Nervous System: Biosynthesis and Degradation

Cited by 14 publications

References 159 publications

Subregional brain distribution of simple and complex glycosphingolipids in the mucopolysaccharidosis type I (Hurler syndrome) mouse: impact of diet

Subregional brain distribution of simple and complex glycosphingolipids in the mucopolysaccharidosis type I (Hurler syndrome) mouse: impact of diet

Structures, Biosynthesis, and Functions of Gangliosides-an Overview

Functional Roles of Gangliosides in Neurodevelopment: An Overview of Recent Advances

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