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GQ1 Ganglioside

About the structure and biological function of GQ1

Structure. GQ1 ganglioside lipids (GQ1) are a type of gangliosides, a subclass of glycosphingolipids. Their structure consists of a ceramide backbone linked to an oligosaccharide unit made of eight sugar molecules. Four of them are sialic acid. The ceramide backbone contains two hydrocarbon chains: a long-chain base which is linked to a fatty acid via an amide bond. The fatty acid and the long-chain base can be of variable length, hydroxylated, and contain double bonds.

Function. 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 Ganglioside

About the structure and biological function of GT3

Structure. GT3 ganglioside lipids (GT3) are a type of gangliosides, a subclass of glycosphingolipids. Their structure consists of a ceramide backbone linked to an oligosaccharide unit made of five sugar molecules. Three of them are sialic acid. The ceramide backbone contains two hydrocarbon chains: a long-chain base which is linked to a fatty acid via an amide bond. The fatty acid and the long-chain base can be of variable length, hydroxylated, and contain double bonds.

Function. 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 Ganglioside

About the structure and biological function of GT2

Structure. GT2 ganglioside lipids (GT2) are a type of gangliosides, a subclass of glycosphingolipids. Their structure consists of a ceramide backbone linked to an oligosaccharide unit made of six sugar molecules. Three of them are sialic acid. The ceramide backbone contains two hydrocarbon chains: a long-chain base which is linked to a fatty acid via an amide bond. The fatty acid and the long-chain base can be of variable length, hydroxylated, and contain double bonds.

Function. 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 Ganglioside

About the structure and biological function of GT1

Structure. GT1 ganglioside lipids (GT1) are a type of gangliosides, a subclass of glycosphingolipids. Their structure consists of a ceramide backbone linked to an oligosaccharide unit made of seven sugar molecules. Three of them are sialic acid. The ceramide backbone contains two hydrocarbon chains: a long-chain base which is linked to a fatty acid via an amide bond. The fatty acid and the long-chain base can be of variable length, hydroxylated, and contain double bonds.

Function. 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. Further, GT1 gangliosides act as the receptor for the tetanus toxin and further neurotoxins.

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GM4 Ganglioside

About the structure and biological function of GM4

Structure. GM4 ganglioside lipids (GM4) are a type of gangliosides, a subclass of glycosphingolipids. Their structure consists of a ceramide backbone linked to a disaccharide unit. One of them is a sialic acid. The ceramide backbone contains two hydrocarbon chains: a long-chain base which is linked to a fatty acid via an amide bond. The fatty acid and the long-chain base can be of variable length, hydroxylated, and contain double bonds.

Function. 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, 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 Ganglioside

About the structure and biological function of GM3

Structure. GM3 ganglioside lipids (GM3) are a type of gangliosides, a subclass of glycosphingolipids. Their structure consists of a ceramide backbone linked to an oligosaccharide unit made of three sugar molecules. One of them is a sialic acid. The ceramide backbone contains two hydrocarbon chains: a long-chain base which is linked to a fatty acid via an amide bond. The fatty acid and the long-chain base can be of variable length, hydroxylated, and contain double bonds.

Function. 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 concentration of GM3 in caveolae affects the activity of receptors involved in the regulation of glucose uptake. 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 Ganglioside

About the structure and biological function of GM2

Structure. GM2 ganglioside lipids (GM2) are a type of gangliosides, a subclass of glycosphingolipids. Their structure consists of a ceramide backbone linked to an oligosaccharide unit made of four sugar molecules. One of them is a sialic acid. The ceramide backbone contains two hydrocarbon chains: a long-chain base which is linked to a fatty acid via an amide bond. The fatty acid and the long-chain base can be of variable length, hydroxylated, and contain double bonds.

Function. 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 Ganglioside

About the structure and biological function of GM1

Structure. GM1 ganglioside lipids (monosialotetrahexosylgangliosides, GM1) are a type of gangliosides, a subclass of glycosphingolipids. Their structure consists of a ceramide backbone linked to an oligosaccharide unit made of five sugar molecules. One of them is a sialic acid. The ceramide backbone contains two hydrocarbon chains: a long-chain base which is linked to a fatty acid via an amide bond. The fatty acid and the long-chain base can be of variable length, hydroxylated, and contain double bonds.

Function. 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 Ganglioside

About the structure and biological function of GD3

Structure. GD3 ganglioside lipids (GD3) are a type of gangliosides, a subclass of glycosphingolipids. Their structure consists of a ceramide backbone linked to an oligosaccharide unit made of four sugar molecules. Two of them are sialic acid. The ceramide backbone contains two hydrocarbon chains: a long-chain base which is linked to a fatty acid via an amide bond. The fatty acid and the long-chain base can be of variable length, hydroxylated, and contain double bonds.

Function. 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 Ganglioside

About the structure and biological function of GD2

Structure. GD2 ganglioside lipids (GD2) are a type of gangliosides, a subclass of glycosphingolipids. Their structure consists of a ceramide backbone linked to an oligosaccharide unit made of five sugar molecules. Two of them are sialic acid. The ceramide backbone contains two hydrocarbon chains: a long-chain base which is linked to a fatty acid via an amide bond. The fatty acid and the long-chain base can be of variable length, hydroxylated, and contain double bonds.

Function. 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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