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GQ1

About the structure and biological function of GQ1

GQ1 lipids are a type of gangliosides, a subclass of glycosphingolipids. Their structure consists of a ceramide base linked to a tetra-sialic oligosaccharide unit made of eight sugar molecules. The ceramide base contains two hydrocarbon chains, the long-chain base and a fatty acid. GQ1 gangliosides are found in vertebrate cells, especially cells of the nervous system. On a subcellular level, they are enriched in the cell membrane and in lipid rafts.

GQ1 gangliosides belong to the major gangliosides of the mammal brain. In Miller Fisher syndrome, a rare autoimmune nerve disease that is considered to be a variant of Guillain-Barré syndrome, patients have a unique antibody against GQ1 lipids. Patients experience paralysis of ocular muscles, absence of reflexes, and lack of voluntary coordination of muscle movements. Further, GQ1 levels are reduced in Alzheimer’s models and GQ1 gangliosides have been shown to interact with the cholera toxin.

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GT3

About the structure and biological function of GT3

GT3 lipids are a type of gangliosides, a subclass of glycosphingolipids. Their structure consists of a ceramide base linked to a tri-sialic oligosaccharide unit made of five sugar molecules. The ceramide base contains two hydrocarbon chains, the long-chain base and a fatty acid. GT3 gangliosides are found in vertebrate cells, especially cells of the nervous system. On a subcellular level, they are enriched in the cell membrane and in lipid rafts.

Little is known about the function of GT3 gangliosides in vertebrates but they are elevated in the human retina where they are suggested to play a specific role in the structure and function of the tissue. They also serve as precursors of more complex gangliosides. Modified GT3 gangliosides have been associated with tumors, representing an attractive target for immunotherapeutic approaches using GT3 ganglioside antibodies. Further, GT3 levels are reduced in Alzheimer disease models.

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GT2

About the structure and biological function of GT2

GT2 lipids are a type of gangliosides, a subclass of glycosphingolipids. Their structure consists of a ceramide base linked to a tri-sialic oligosaccharide unit made of six sugar molecules. The ceramide base contains two hydrocarbon chains, the long-chain base and a fatty acid. GT2 gangliosides are found in vertebrate cells, especially cells of the nervous system. On a subcellular level, they are enriched in the cell membrane and in lipid rafts.

Little is known about the function of GT2 gangliosides in vertebrates but modified GT2 lipids have been associated with tumors. This represents an attractive target for immunotherapeutic approaches using specific GT2 antibodies. They also serve as the direct precursors of the more complex GT1 gangliosides. Further, GT2 gangliosides have been shown to interact with the tetanus toxin facilitating entry of the toxin into the cell.

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GT1

About the structure and biological function of GT1

GT1 lipids are a type of gangliosides, a subclass of glycosphingolipids. Their structure consists of a ceramide base linked to a tri-sialic oligosaccharide unit made of seven sugar molecules. The ceramide base contains two hydrocarbon chains, the long-chain base and a fatty acid. GT1 gangliosides are found in vertebrate cells, especially cells of the nervous system. On a subcellular level, they are enriched in the cell membrane and in lipid rafts.

GT1 gangliosides belong to the major gangliosides of the mammal brain. Within the cell membrane of the axons of neurons, GT1 lipids bind to the myelin-associated glycoprotein, a membrane protein of the innermost myelin membrane wrap. This interaction maintains and regulates axon-myelin stability. They also inhibit the binding of interferon type 1 activity. Further, GT1 gangliosides act as the receptor for the tetanus toxin and the botulinum toxin.

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GM4

About the structure and biological function of GM4

GM4 lipids are a type of gangliosides, a subclass of glycosphingolipids. Their structure consists of a ceramide base linked to a mono-sialic disaccharide unit. The ceramide base contains two hydrocarbon chains, the long-chain base and a fatty acid. GM4 gangliosides are found invertebrates, especially in nervous tissue and kidney. On a subcellular level, they are enriched in the cell membrane and in lipid rafts.

Little is known about the function of GM4 gangliosides in vertebrates but they have been found to be a major ganglioside within myelin, the insulating layer that is produced by oligodendrocytes and forms around the axons of neurons. GM4 lipids are increased in the frontal cortex of Alzheimer’s patients. Further, administration of GM4 supports oligodendrocyte proliferation, a process that is important for  remyelination of demyelinated neurons and is impaired in multiple sclerosis.

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GM3

About the structure and biological function of GM3

GM3 lipids are a type of gangliosides, a subclass of glycosphingolipids. Their structure consists of a ceramide base linked to a mono-sialic oligosaccharide unit made of three sugar molecules. The ceramide base contains two hydrocarbon chains, the long-chain base and a fatty acid. GM3 gangliosides are found in vertebrates, especially in nervous tissue and the intestine. On a subcellular level, they are enriched in the cell membrane and in lipid rafts.

GM3 lipids are the simplest gangliosides chemically and  serve as precursors of more complex gangliosides but also fulfill a structural role themselves. In the cell membrane, they associate with each other and other lipids into lipid rafts and caveolae. The activity of insulin receptors in caveolae and thus insulin resistance is controlled by the concentration of GM3. They also are critical for cochlear hair cells and essential for hearing. Further, modified GM3 lipids are found in many cancers, including melanomas and stage II breast cancers.

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GM2

About the structure and biological function of GM2

GM2 lipids are a type of gangliosides, a subclass of glycosphingolipids. Their structure consists of a ceramide base linked to a mono-sialic oligosaccharide unit made of four sugar molecules. The ceramide base contains two hydrocarbon chains, the long-chain base and a fatty acid. GM2 gangliosides are found in vertebrate cells, especially in nervous tissue and bone marrow. On a subcellular level, they are enriched in the cell membrane and in lipid rafts.

GM2 gangliosides are components of the cell membrane and may suppress malignant properties of various cancers. The mechanism is suggested to be due to complex formation at the cell surface with membrane proteins. Genetic defects leading to accumulation of GM2, due to increased lysosomal storage  cause Tay-Sachs, Sandhoff and AB variant disease. Further, GM2 lipids bind to a toxin secreted by Clostridium perfringens.

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GM1

About the structure and biological function of GM1

GM1 lipids are a type of gangliosides, a subclass of glycosphingolipids. Their structure consists of a ceramide base linked to a mono-sialic oligosaccharide unit made of five sugar molecules. The ceramide base contains two hydrocarbon chains, the long-chain base and a fatty acid. GM1 gangliosides are found in vertebrate cells, especially cells of the nervous system. On a subcellular level, they are enriched in the cell membrane and in lipid rafts.

GM1 gangliosides promote differentiation of various neuronal cells. They have protective effects on the neural system by supporting neural stem cell survival and proliferation, regeneration of axons, and inhibiting neurodegeneration through autophagy, cellular “self-eating”. In lipid rafts, GM1 lipids serve a key role in several signaling systems. However, GM1 lipids also act as specific receptors for the cholera toxin. GM1  accumulation leads to GM1 gangliosidosis, a lysosomal storage disease  causing generalized symptoms including  mental retardation.

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GD3

About the structure and biological function of GD3

GD3 lipids are a type of gangliosides, a subclass of glycosphingolipids. Their structure consists of a ceramide base linked to a di-sialic oligosaccharide unit made of four sugar molecules. The ceramide base contains two hydrocarbon chains, the long-chain base and a fatty acid. GD3 gangliosides are found in vertebrate cells, especially cells of the nervous system. On a subcellular level, they are enriched in the cell membrane and in lipid rafts.

GD3 gangliosides are fundamental in neurogenesis. They bind to the EGF receptor resulting in the activation of a signaling cascade promoting cell proliferation. This is essential for stem cell self-renewal in the brain. GD3 lipids are critical for apoptosis and autophagy, programmed cell death and cellular “self-eating”. They also serve as precursors of more complex gangliosides. Further, GD3 levels are elevated in melanomas and neuroblastomas, and they are the main gangliosides in early human breast milk.

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GD2

About the structure and biological function of GD2

GD2 lipids are a type of gangliosides, a subclass of glycosphingolipids. Their structure consists of a ceramide base linked to a di-sialic oligosaccharide unit made of five sugar molecules. The ceramide base contains two hydrocarbon chains, the long-chain base and a fatty acid. GD2 gangliosides are found in vertebrate cells, especially cells of the nervous system. On a subcellular level, they are enriched in the cell membrane and in lipid rafts.

GD2 gangliosides have been linked to many cancers. While only present in trace amounts in normal tissues, GD2 lipids are found at much higher concentrations in cancer cells, especially in melanomas and neuroblastomas. They are considered tumor-associated antigens and the enzyme GD2 synthase is investigated as potential drug target. In neuroblastoma, a GD2 antibody has been approved for treatment in combination with other drugs but they also serve as circulating biomarkers.

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