Guillain-Barré syndrome (GBS) is an acute autoimmune neuropathy, often preceded by an infection. Serum anti-ganglioside antibodies are frequently elevated in titer. Those antibodies are useful for diagnosis. Some of them also may be directly involved in the pathogenetic mechanisms by binding to the regions where the respective target ganglioside is specifically localized. We have recently found the presence of the antibody that specifically recognizes a new conformational epitope formed by two gangliosides (ganglioside complex) in the acute-phase sera of some GBS patients. In particular, the antibodies against GD1a/GD1b and/or GD1b/GT1b complexes are associated with severe GBS requiring artificial ventilation. Some patients with Miller Fisher syndrome also have antibodies against ganglioside complexes including GQ1b; such as GQ1b/GM1 and GQ1b/GD1a. Gangliosides along with other components as cholesterol are known to form lipid rafts, in which the carbohydrate portions of two different gangliosides may form a new conformational epitope. Within the rafts, gangliosides are considered to interact with important receptors or signal transducers. The antibodies against ganglioside complexes may therefore directly cause nerve conduction failure and severe disability in GBS. More study is needed to elucidate the roles of the antibodies against ganglioside complexes.
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http://dx.doi.org/10.1016/j.bbagen.2007.10.001 | DOI Listing |
Neurobiol Dis
February 2025
Vulnerable Brain Lab, Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, Western University, London, Ontario N6A 5C1, Canada. Electronic address:
Alzheimer's disease (AD) is a progressive neurodegenerative disease that accounts for two-thirds of all dementia cases, and age is the strongest risk factor. In addition to the amyloid hypothesis, lipid dysregulation is now recognized as a core component of AD pathology. Gangliosides are a class of membrane lipids of the glycosphingolipid family and are enriched in the central nervous system (CNS).
View Article and Find Full Text PDFCells
January 2025
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK.
Sandhoff disease (SD) is a progressive neurodegenerative lysosomal storage disorder characterized by GM2 ganglioside accumulation as a result of mutations in the gene, which encodes the β-subunit of the enzyme β-hexosaminidase. Lysosomal storage of GM2 triggers inflammation in the CNS and periphery. The NLRP3 inflammasome is an important coordinator of pro-inflammatory responses, and we have investigated its regulation in murine SD.
View Article and Find Full Text PDFIn Vivo
December 2024
Department of Pharmacology, School of Dentistry, Aichi Gakuin University, Nagoya, Japan;
Background/aim: Gangliosides regulate bone formation and resorption. Bone formation is reduced in mice lacking ganglioside GM2/GD2 synthase due to a decrease in osteoblasts. However, the effects of the loss of complex gangliosides by the deletion of both GM2/GD2 and GD3 synthases are unknown.
View Article and Find Full Text PDFLiver Int
January 2025
Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
Background & Aims: GD2, a member of the ganglioside (GS) family (sialic acid-containing glycosphingolipids), is a potential biomarker of cancer stem cells (CSC) in several tumours. However, the possible role of GD2 and its biosynthetic enzyme, GD3 synthase (GD3S), in intrahepatic cholangiocarcinoma (iCCA) has not been explored.
Methods: The stem-like subset of two iCCA cell lines was enriched by sphere culture (SPH) and compared to monolayer parental cells (MON).
Angew Chem Int Ed Engl
December 2024
Key Laboratory of Marine Drugs of Ministry of Education, Shandong Key Laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China.
Owing to the inaccessibility of β1-4-N-acetylgalactosaminyltransferase for direct glycan chain elongation, the enzymatic synthesis of 0-series gangliosides with extended backbones has not been explored. In this study, sialic acid was enzymatically introduced as an auxiliary group to overcome the limitation of substrate specificity of Campylobacter jejuni β1-4-N-acetylgalactosaminyltransferase (CjCgtA) to achieve the synthesis of desired extended 0-series ganglioside core structures, and the sialic acid auxiliary group could be removed by sialidase at appropriate stages. A bacterial α2-6-sialyltransferase from Photobacterium damselae (Pd2,6ST) exhibited unexpected acceptor substrate specificity for 0-series ganglioside core structures, providing ready access to complex gangliosides bearing the sialyl N-acetylgalactosamine unit.
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