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Essays in Biochemistry Sep 2020Lyso-glycosphingolipids are generated in excess in glycosphingolipid storage disorders. In the course of these pathologies glycosylated sphingolipid species accumulate... (Review)
Review
Lyso-glycosphingolipids are generated in excess in glycosphingolipid storage disorders. In the course of these pathologies glycosylated sphingolipid species accumulate within lysosomes due to flaws in the respective lipid degrading machinery. Deacylation of accumulating glycosphingolipids drives the formation of lyso-glycosphingolipids. In lysosomal storage diseases such as Gaucher Disease, Fabry Disease, Krabbe disease, GM1 -and GM2 gangliosidosis, Niemann Pick type C and Metachromatic leukodystrophy massive intra-lysosomal glycosphingolipid accumulation occurs. The lysosomal enzyme acid ceramidase generates the deacylated lyso-glycosphingolipid species. This review discusses how the various lyso-glycosphingolipids are synthesized, how they may contribute to abnormal immunity in glycosphingolipid storing lysosomal diseases and what therapeutic opportunities exist.
Topics: Acid Ceramidase; Animals; Enzyme Replacement Therapy; Genetic Therapy; Glycosphingolipids; Humans; Immunity; Lysosomal Storage Diseases; Lysosomes; Molecular Targeted Therapy
PubMed: 32808655
DOI: 10.1042/EBC20190090 -
Chembiochem : a European Journal of... Jul 2023Glycosphingolipid (GSL) and glycosylphosphatidylinositol (GPI) are the two major glycolipids expressed by eukaryotic cells, and their metabolisms share the same... (Review)
Review
Glycosphingolipid (GSL) and glycosylphosphatidylinositol (GPI) are the two major glycolipids expressed by eukaryotic cells, and their metabolisms share the same machineries. Moreover, both GSLs and GPI-anchored proteins (GPI-APs) are localized in the cholesterol-rich regions, namely the lipid rafts, of the cell membrane, where many other signaling molecules are compartmentalized as well. Therefore, the interaction between GSLs and GPI-APs and their interactions with other molecules in the lipid rafts are inevitable. This review is focused on the influences of GSLs and GPI-APs on each other's biosynthesis, trafficking, cell membrane distribution, and biological functions, such as signal transduction.
Topics: Glycosphingolipids; Glycosylphosphatidylinositols; Cell Membrane; Proteins; Membrane Microdomains
PubMed: 36935354
DOI: 10.1002/cbic.202200761 -
Molecular Neurodegeneration Oct 2020Parkinson's disease is a progressive neurodegenerative disease characterized by the loss of dopaminergic neurons of the nigrostriatal pathway and the formation of... (Review)
Review
Parkinson's disease is a progressive neurodegenerative disease characterized by the loss of dopaminergic neurons of the nigrostriatal pathway and the formation of neuronal inclusions known as Lewy bodies. Chronic neuroinflammation, another hallmark of the disease, is thought to play an important role in the neurodegenerative process. Glycosphingolipids are a well-defined subclass of lipids that regulate crucial aspects of the brain function and recently emerged as potent regulators of the inflammatory process. Deregulation in glycosphingolipid metabolism has been reported in Parkinson's disease. However, the interrelationship between glycosphingolipids and neuroinflammation in Parkinson's disease is not well known. This review provides a thorough overview of the links between glycosphingolipid metabolism and immune-mediated mechanisms involved in neuroinflammation in Parkinson's disease. After a brief presentation of the metabolism and function of glycosphingolipids in the brain, it summarizes the evidences supporting that glycosphingolipids (i.e. glucosylceramides or specific gangliosides) are deregulated in Parkinson's disease. Then, the implications of these deregulations for neuroinflammation, based on data from human inherited lysosomal glycosphingolipid storage disorders and gene-engineered animal studies are outlined. Finally, the key molecular mechanisms by which glycosphingolipids could control neuroinflammation in Parkinson's disease are highlighted. These include inflammasome activation and secretion of pro-inflammatory cytokines, altered calcium homeostasis, changes in the blood-brain barrier permeability, recruitment of peripheral immune cells or production of autoantibodies.
Topics: Animals; Brain; Glycosphingolipids; Humans; Inflammation; Parkinson Disease
PubMed: 33069254
DOI: 10.1186/s13024-020-00408-1 -
Glycoconjugate Journal Dec 2017The application of human stem cell technology offers theoretically a great potential to treat various human diseases. However, to achieve this goal a large number of... (Review)
Review
The application of human stem cell technology offers theoretically a great potential to treat various human diseases. However, to achieve this goal a large number of scientific issues remain to be solved. Cell surface carbohydrate antigens are involved in a number of biomedical phenomena that are important in clinical applications of stem cells, such as cell differentiation and immune reactivity. Due to their cell surface localization, carbohydrate epitopes are ideally suited for characterization of human pluripotent stem cells. Amongst the most commonly used markers to identify human pluripotent stem cells are the globo-series glycosphingolipids SSEA-3 and SSEA-4. However, our knowledge regarding human pluripotent stem cell glycosphingolipid expression was until recently mainly based on immunological assays of intact cells due to the very limited amounts of cell material available. In recent years the knowledge regarding glycosphingolipids in human embryonic stem cells has been extended by biochemical studies, which is the focus of this review. In addition, the distribution of the human pluripotent stem cell glycosphingolipids in human tissues, and glycosphingolipid changes during human stem cell differentiation, are discussed.
Topics: Blood Group Antigens; Embryonic Stem Cells; Glycosphingolipids; Humans; Stage-Specific Embryonic Antigens
PubMed: 27325407
DOI: 10.1007/s10719-016-9706-y -
Cold Spring Harbor Perspectives in... Jul 2011The combination of carbohydrate and lipid generates unusual molecules in which the two distinctive halves of the glycoconjugate influence the function of each other.... (Review)
Review
The combination of carbohydrate and lipid generates unusual molecules in which the two distinctive halves of the glycoconjugate influence the function of each other. Membrane glycolipids can act as primary receptors for carbohydrate binding proteins to mediate transmembrane signaling despite restriction to the outer bilayer leaflet. The extensive heterogeneity of the lipid moiety plays a significant, but still largely unknown, role in glycosphingolipid function. Potential interplay between glycolipids and their fatty acid isoforms, together with their preferential interaction with cholesterol, generates a complex mechanism for the regulation of their function in cellular physiology.
Topics: Animals; Ceramides; Embryonic Development; Glycosphingolipids; HIV Envelope Protein gp120; HIV-1; Membrane Microdomains; Mice; Molecular Conformation; Protein Transport; Receptors, Cell Surface; Signal Transduction; Toxins, Biological
PubMed: 21555406
DOI: 10.1101/cshperspect.a004788 -
International Journal of Molecular... May 2023GM1 is one of the major glycosphingolipids (GSLs) on the cell surface in the central nervous system (CNS). Its expression level, distribution pattern, and lipid... (Review)
Review
GM1 is one of the major glycosphingolipids (GSLs) on the cell surface in the central nervous system (CNS). Its expression level, distribution pattern, and lipid composition are dependent upon cell and tissue type, developmental stage, and disease state, which suggests a potentially broad spectrum of functions of GM1 in various neurological and neuropathological processes. The major focus of this review is the roles that GM1 plays in the development and activities of brains, such as cell differentiation, neuritogenesis, neuroregeneration, signal transducing, memory, and cognition, as well as the molecular basis and mechanisms for these functions. Overall, GM1 is protective for the CNS. Additionally, this review has also examined the relationships between GM1 and neurological disorders, such as Alzheimer's disease, Parkinson's disease, GM1 gangliosidosis, Huntington's disease, epilepsy and seizure, amyotrophic lateral sclerosis, depression, alcohol dependence, etc., and the functional roles and therapeutic applications of GM1 in these disorders. Finally, current obstacles that hinder more in-depth investigations and understanding of GM1 and the future directions in this field are discussed.
Topics: Humans; G(M1) Ganglioside; Gangliosidosis, GM1; Central Nervous System; Brain; Glycosphingolipids
PubMed: 37298512
DOI: 10.3390/ijms24119558 -
International Journal of Molecular... Aug 2020Lipid rafts are dynamic assemblies of glycosphingolipids, sphingomyelin, cholesterol, and specific proteins which are stabilized into platforms involved in the... (Review)
Review
Lipid rafts are dynamic assemblies of glycosphingolipids, sphingomyelin, cholesterol, and specific proteins which are stabilized into platforms involved in the regulation of vital cellular processes. The rafts at the cell surface play important functions in signal transduction. Recent reports have demonstrated that lipid rafts are spatially and compositionally heterogeneous in the single-cell membrane. In this review, we summarize our recent data on living platelets using two specific probes of raft components: lysenin as a probe of sphingomyelin-rich rafts and BCθ as a probe of cholesterol-rich rafts. Sphingomyelin-rich rafts that are spatially and functionally distinct from the cholesterol-rich rafts were found at spreading platelets. Fibrin is translocated to sphingomyelin-rich rafts and platelet sphingomyelin-rich rafts act as platforms where extracellular fibrin and intracellular actomyosin join to promote clot retraction. On the other hand, the collagen receptor glycoprotein VI is known to be translocated to cholesterol-rich rafts during platelet adhesion to collagen. Furthermore, the functional roles of platelet glycosphingolipids and platelet raft-binding proteins including G protein-coupled receptors, stomatin, prohibitin, flotillin, and HflK/C-domain protein family, tetraspanin family, and calcium channels are discussed.
Topics: Animals; Blood Platelets; Cell Membrane; Cholesterol; Fibrin; Glycosphingolipids; Humans; Membrane Microdomains; Signal Transduction; Sphingomyelins
PubMed: 32748854
DOI: 10.3390/ijms21155539 -
The Journal of Biological Chemistry Nov 1986Acid and non-acid glycosphingolipids of stomach, small and large intestine, and stimulated feces of germ-free and conventional rats of the same stain have been isolated... (Comparative Study)
Comparative Study
Acid and non-acid glycosphingolipids of stomach, small and large intestine, and stimulated feces of germ-free and conventional rats of the same stain have been isolated and characterized. The glycosphingolipid patterns of the intestinal organs were chemically and immunologically very similar between the two groups of rats and relatively unaffected by the presence of an intestinal microbial flora. The major exception was the presence of hematoside with N-glycoloylneuraminic acid (NeuGc) (NeuGc alpha 2----3Gal beta 1----4Glc beta 1----1Cer) in the stomach of conventional rats not found in the stomach of germ-free animals. Glycosphingolipids of stimulated feces of germ-free animals were derived from epithelial cells mainly of the small intestine and showed no signs of degradation. Glycosphingolipids of feces of conventional rats completely retained the pattern of blood group A-, B-, and H-active glycolipids as found in sterile feces but contained less of hematoside and more of lactosylceramide. This effect was probably due to degradation by bacteria, as demonstrated in vitro with the production of lactosylceramide after treatment of the isolated acid glycolipids of sterile feces with neuraminidase from Clostridium perfringens. The amount of total non-acid glycosphingolipids per dry weight was similar for stomach, was 50% higher for small intestine, and 300% higher for large intestine of germ-free animals compared to conventional animals. Due to the presence of large amounts of mucins the dry sterile feces contained 12% less non-acid glycolipids than conventional feces. However, calculated per rat per day the germ-free animal excreted more of non-acid glycosphingolipids (1.8 and 1.2 mg, respectively).
Topics: Animals; Carbohydrate Conformation; Carbohydrate Sequence; Chromatography, Thin Layer; Feces; Female; Germ-Free Life; Glycolipids; Glycosphingolipids; Intestine, Large; Intestine, Small; Neuraminidase; Rats; Rats, Inbred Strains; Stomach
PubMed: 3771576
DOI: No ID Found -
Discovery Medicine Apr 2011Much remains unknown about basic aspects of HIV-1 infection and cell susceptibility. Glycosphingolipid (GSL) binding by the HIV-1 adhesin gp120 has long been implicated... (Review)
Review
Much remains unknown about basic aspects of HIV-1 infection and cell susceptibility. Glycosphingolipid (GSL) binding by the HIV-1 adhesin gp120 has long been implicated in the infection of non-lymphoid cells, as well as CD4(+) T cells and monocytes, the primary targets of HIV-1 infection. We have identified the P(k) blood group antigen (a GSL) globotriaosylceramide (Gb(3)) as a new resistance effector against HIV-1 infection. Significantly, the α-galactosyltransferase (A4GALT, Gb(3) synthase) responsible for the synthesis of Gb(3) is included among markers genetically linked to HIV-1 resistance. Other GSLs, including GalCer and GM3, have been implicated as facilitators of HIV infection. This review will address the role of GSLs in HIV/AIDS but focus on the role of Gb(3) as a newly described natural resistance factor for the prevention of HIV infection and examine potential therapies that would utilize soluble analogues of this unique GSL.
Topics: Acquired Immunodeficiency Syndrome; Animals; Cell Fusion; Glycosphingolipids; Humans; Membrane Microdomains; Receptors, Virus; Virus Internalization
PubMed: 21524384
DOI: No ID Found -
Journal of Lipid Research Feb 1978
Review
Topics: ABO Blood-Group System; Animals; Blood Group Antigens; Erythrocytes; Fucose; Gastric Mucosa; Glycosphingolipids; Humans; Intestinal Mucosa; Molecular Conformation; Oligosaccharides; Swine
PubMed: 344823
DOI: No ID Found