New approach for glyco‐ and lipidomics – Molecular scanning of human brain gangliosides by TLC‐Blot and MALDI‐QIT‐TOF MS

Valdes-Gonzalez, Tania; Goto‐Inoue, Naoko; Hirano, Wakako; Ishiyama, H.; Hayasaka, Takahiro; Setou, Mitsutoshi; Taki, Takao

doi:10.1111/j.1471-4159.2010.07152.x

Cited by 61 publications

(53 citation statements)

References 30 publications

(51 reference statements)

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“…Analytical tools for studying gangliosides have improved significantly, but ganglioside analysis remains largely the purview of specialists in the field [90,91]. The simplest analytical tools to use, ganglioside-specific antibodies and binding proteins (toxins) are widely available and provide enhanced opportunities to study brain ganglioside expression and function in health and disease [92–95].…”

Section: Tools and Challenges In Ganglioside Researchmentioning

confidence: 99%

“…Thin-layer chromatography of gangliosides is relatively simple and sensitive [99], whereas techniques for MS analysis of isolated gangliosides require expensive equipment and advanced expertise, but are much more powerful, providing detailed qualitative and quantitative information by electrospray MS n techniques on relatively small samples [90,91,100]. …”

Section: Tools and Challenges In Ganglioside Researchmentioning

confidence: 99%

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Gangliosides of the Vertebrate Nervous System

Schnaar

2016

Journal of Molecular Biology

166

143

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Gangliosides, sialylated glycosphingolipids found on all vertebrate cells and tissues, are major molecular determinants on the surfaces of vertebrate nerve cells. Comprised of a sialylated glycan attached to a ceramide lipid, the same four structures – GM1, GD1a, GD1b and GT1b – represent the vast majority (>90%) of gangliosides in the brains of all mammals and birds. Primarily found on the outer surface of the plasma membrane with their glycans facing outward, gangliosides associate laterally with each other, sphingomyelin, cholesterol, and select proteins in lipid rafts – dynamic functional subdomains of the plasma membrane. The functions of gangliosides in the human nervous system are revealed by congenital mutations in ganglioside biosynthetic genes. Mutations in ST3GAL5, which codes for an enzyme early in brain ganglioside biosynthesis, results in an early-onset seizure disorder with profound motor and cognitive decay, whereas mutations in B4GALNT1, a gene encoding a later step, result in hereditary spastic paraplegia accompanied by intellectual deficits. The molecular functions of brain gangliosides include regulation of receptors in the same membrane via lateral (cis) associations and regulation of cell-cell recognition by trans interaction with ganglioside binding proteins on apposing cells. Gangliosides also affect aggregation of Aβ (Alzheimer’s disease) and α-synuclein (Parkinson’s Disease). As analytical, biochemical and genetic tools advance, research on gangliosides promises to reveal mechanisms of molecular control related to nerve and glial cell differentiation, neuronal excitability, axon outgrowth after nervous system injury, and protein folding in neurodegenerative diseases.

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Section: Tools and Challenges In Ganglioside Researchmentioning

confidence: 99%

Section: Tools and Challenges In Ganglioside Researchmentioning

confidence: 99%

Gangliosides of the Vertebrate Nervous System

Schnaar

2016

Journal of Molecular Biology

166

143

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“…The apparent contradiction might be resolved on the basis of Ab removing GM1 from its functional associations with membrane proteins, which are then restored by GM1 replacement with the infusion. Of further interest were the findings that GM1 and other gangliosides are expressed at deficient levels in various brain regions relative to age-matched controls, including early-onset [109] and advanced-stage [110][111][112] forms of AD. Adding to this conflicted story was the interesting finding that GD3 synthase elimination in a double-transgenic (APP/PSEN1) mouse model of AD elevated GM1 and GD1a while removing GD3 and other b-series gangliosides, and almost completely eliminated both aggregated and unaggregated Ab and associated neuropathology [113].…”

Section: Gm1 In Neurological Disordersmentioning

confidence: 99%

The multi-tasked life of GM1 ganglioside, a true factotum of nature

Ledeen

2015

Trends in Biochemical Sciences

191

186

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“…Accordingly, we performed a detailed comparison of the ganglioside compositions and their molecular species between neural disease patients and control patients. 18) Figure 3 shows a chromatographic profile of total lipids from the gray matter areas of the hippocampi of patients with Alzheimer's disease, Parkinson's disease and control patients. The TLC clearly shows that the levels of b-series gangliosides, GD1b and GT1b, in patients with Alzheimer's disease were lower than those in patients with Parkinson's disease.…”

Section: Tlc-blot/maldi-tof Msmentioning

confidence: 99%

An Approach to Glycobiology from Glycolipidomics: Ganglioside Molecular Scanning in the Brains of Patients with Alzheimer’s Disease by TLC-Blot/Matrix Assisted Laser Desorption/Ionization-Time of Flight MS

Taki

2012

Biological & Pharmaceutical Bulletin

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We have established a new approach to glyco-and lipidomics using a thin layer chromatography (TLC)-Blot/matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry (MS) system. This new approach consists of a combination of a method for transferring lipids separated on a TLC-plate to a poly-vinylidene difluoride (PVDF) membrane and direct mass spectrometric analysis of the individual lipids on the membrane by ion trap-type MALDI-TOF MS. This technology was applied to the analysis of individual lipids from the human brain. Then, based on the results of this analysis, ganglioside molecular species in neural diseases were analyzed. The levels of gangliosides GD1b and GT1b were lower in the hippocampal gray matter of patients with Alzheimer's disease than in the hippocampal gray matter of patients with Parkinson's disease or the control patients. The molecular scanning of individual ganglioside molecular species showed a significant reduction of d20 : 1/C18 : 0 ceramide-containing gangliosides in patients with Alzheimer's disease. These findings suggest that Alzheimer's disease is a kind of ganglioside metabolic disease affecting the hippocampal area. A new approach to glycobiology by the TLC-Blot/ MALDI-TOF MS system is proposed.

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New approach for glyco‐ and lipidomics – Molecular scanning of human brain gangliosides by TLC‐Blot and MALDI‐QIT‐TOF MS

Cited by 61 publications

References 30 publications

Gangliosides of the Vertebrate Nervous System

Gangliosides of the Vertebrate Nervous System

The multi-tasked life of GM1 ganglioside, a true factotum of nature

An Approach to Glycobiology from Glycolipidomics: Ganglioside Molecular Scanning in the Brains of Patients with Alzheimer’s Disease by TLC-Blot/Matrix Assisted Laser Desorption/Ionization-Time of Flight MS

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