The Experts below are selected from a list of 276 Experts worldwide ranked by ideXlab platform
Ronald L Schnaar - One of the best experts on this subject based on the ideXlab platform.
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An anti-Ganglioside antibody-secreting hybridoma induces neuropathy in mice.
Annals of neurology, 2004Co-Authors: Kazim A. Sheikh, Ronald L Schnaar, Gang Zhang, Yanpin Gong, John W. GriffinAbstract:Immune responses against Gangliosides are strongly implicated in the pathogenesis of some variants of Guillain-Barre syndrome (GBS). For example, IgG antibodies against GM1, GD1a, and related Gangliosides are frequently present in patients with post-Campylobacter acute motor axonal neuropathy (AMAN) variant of GBS, and immunization of rabbits with GM1 has produced a model of AMAN. However, the role of anti-Ganglioside antibodies in GBS continues to be debated because of lack of a passive transfer model. We recently have raised several monoclonal IgG anti-Ganglioside antibodies. We passively transfer these antibodies by intraperitoneal hybridoma implantation and by systemic administration of purified anti-Ganglioside antibodies in mice. Approximately half the animals implanted with an intraperitoneal clone of anti-Ganglioside antibody-secreting hybridoma developed a patchy, predominantly axonal neuropathy affecting a small proportion of nerve fibers. In contrast to hybridoma implantation, passive transfer with systemically administered anti-Ganglioside antibodies did not cause nerve fiber degeneration despite high titre circulating antibodies. Blood-nerve barrier studies indicate that animals implanted with hybridoma had leaky blood-nerve barrier compared to mice that received systemically administered anti-Ganglioside antibodies. Our findings suggest that in addition to circulating antibodies, factors such as antibody accessibility and nerve fiber resistance to antibody-mediated injury play a role in the development of neuropathy.
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Gangliosides are functional nerve cell ligands for myelin associated glycoprotein mag an inhibitor of nerve regeneration
Proceedings of the National Academy of Sciences of the United States of America, 2002Co-Authors: Alka A Vyas, Himatkumar V Patel, Susan E Fromholt, Marija Hefferlauc, Kavita A Vyas, Jiyoung M Dang, Melitta Schachner, Ronald L SchnaarAbstract:Myelin-associated glycoprotein (MAG) binds to the nerve cell surface and inhibits nerve regeneration. The nerve cell surface ligand(s) for MAG are not established, although sialic acid-bearing glycans have been implicated. We identify the nerve cell surface Gangliosides GD1a and GT1b as specific functional ligands for MAG-mediated inhibition of neurite outgrowth from primary rat cerebellar granule neurons. MAG-mediated neurite outgrowth inhibition is attenuated by (i) neuraminidase treatment of the neurons; (ii) blocking neuronal Ganglioside biosynthesis; (iii) genetically modifying the terminal structures of nerve cell surface Gangliosides; and (iv) adding highly specific IgG-class antiGanglioside mAbs. Furthermore, neurite outgrowth inhibition is mimicked by highly multivalent clustering of GD1a or GT1b by using precomplexed antiGanglioside Abs. These data implicate the nerve cell surface Gangliosides GD1a and GT1b as functional MAG ligands and suggest that the first step in MAG inhibition is multivalent Ganglioside clustering.
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high affinity anti Ganglioside igg antibodies raised in complex Ganglioside knockout mice reexamination of gd1a immunolocalization
Journal of Neurochemistry, 2001Co-Authors: Michael P Lunn, Alka A Vyas, Susan E Fromholt, Ronald L Schnaar, John W. Griffin, Laurelle A Johnson, Saki Itonori, Jian Huang, James E K HildrethAbstract:Gangliosides, sialic acid-bearing glycosphingolipids, are highly enriched in the vertebrate nervous system. Anti-Ganglioside antibodies are associated with various human neuropathies, although the pathogenicity of these antibodies remains unproven. Testing the pathogenic role of anti-Ganglioside antibodies will be facilitated by developing high-affinity IgG-class complement-fixing monoclonal anti-bodies against major brain Gangliosides, a goal that has been difficult to achieve. In this study, mice lacking complex Gangliosides were used as immune-naive hosts to raise anti-Ganglioside antibodies. Wild-type mice and knockout mice with a disrupted gene for GM2/GD2 synthase (UDP-N-acetyl-D-galactosamine : GM3/GD3 N-acetyl-D-glactosaminyltransferase) were immunized with GD1a conjugated to keyhole limpet hemocyanin. The knockout mice produced a vigorous anti-GD1a IgG response, whereas wildtype littermates failed to do so. Fusion of spleen cells from an immunized knockout mouse with myeloma cells yielded numerous IgG anti-GD1a antibody-producing colonies. Ganglioside binding studies revealed two specificity classes; one colony representing each class was cloned and characterized. High-affinity monoclonal antibody was produced by each hybridoma : an IgG1 that bound nearly exclusively to GD1a and an IgG2b that bound GD1a, GT1b, and GT1aalpha. Both antibodies readily readily detected Gangliosides via ELISA, TLC immune overlay, immunohistochemistry, and immunocytochemistry. In contrast to prior reports using anti-GD1a and anti-GT1b IgM class monoclonal antibodies, the new antibodies bound avidly to granule neurons in brain tissue sections and cell cultures. Mice lacking complex Gangliosides are improved hosts for raising high-affinity, high-titer anti-Ganglioside IgG antibodies for probing for the distribution and physiology of Gangliosides and the pathophysiology of anti-Ganglioside antibodies.
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sialic acid specificity of myelin associated glycoprotein binding
Journal of Biological Chemistry, 1997Co-Authors: Brian E Collins, Lynda J S Yang, Gitali Mukhopadhyay, Marie T Filbin, Makoto Kiso, Akira Hasegawa, Ronald L SchnaarAbstract:Abstract Myelin-associated glycoprotein (MAG), a nervous system cell adhesion molecule, is an I-type lectin that binds to sialylated glycoconjugates, including Gangliosides bearing characteristic structural determinants (Yang, L. J.-S., Zeller, C. B., Shaper, N. L., Kiso, M., Hasegawa, A., Shapiro, R. E., and Schnaar, R. L. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 814-818). Two cell adhesion systems, COS-1 monkey kidney fibroblasts transiently transfected to express MAG and Chinese hamster ovary (CHO) cells stably transfected to express MAG, were used to probe the structural specificity of MAG-Ganglioside binding. Both cell types bound to the same Gangliosides: GQ1bα (IV3NeuAc,III6NeuAc,II3(NeuAc)2-Gg4Cer) > GT1b = GD1a > GM3 > GM1, GD1b, and GQ1b (the latter do not support adhesion). Binding was enhanced by pretreatment of MAG-expressing cells with neuraminidase. MAG-expressing Chinese hamster ovary cells bound directly to Gangliosides resolved on thin layer chromatograms, allowing detection of MAG binding species in a mixture. The simplest Ganglioside ligand for MAG was GM3 bearing N-acetylneuraminic acid, whereas GM3 bearing N-glycolylneuraminic acid did not support adhesion. Chemical modifications of N-acetylneuraminic acid residues (on GD1a) abrogated MAG binding. Mild periodate oxidation of sialic acids to their corresponding seven-carbon (or eight-carbon) sialic acid aldehydes abolished MAG binding, as did further conversion to the corresponding primary alcohols. Eliminating the anionic charge by ethyl esterification, amidation, or reduction also abolished MAG-mediated cell adhesion. These data demonstrate that MAG-Ganglioside binding is highly specific and defines key carbohydrate structural determinants for MAG-mediated cell adhesion to Gangliosides.
Sheng T Hou - One of the best experts on this subject based on the ideXlab platform.
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imaging mass spectrometry detection of Gangliosides species in the mouse brain following transient focal cerebral ischemia and long term recovery
PLOS ONE, 2011Co-Authors: Shawn N Whitehead, Kenneth Chan, Sandhya Gangaraju, Jacqueline Slinn, Sheng T HouAbstract:Gangliosides, a member of the glycosphingolipid family, are heterogeneously expressed in biological membranes and are particularly enriched within the central nervous system. Gangliosides consist of mono- or poly-sialylated oligosaccharide chains of variable lengths attached to a ceramide unit and are found to be intimately involved in brain disease development. The purpose of this study is to examine the spatial profile of Ganglioside species using matrix-assisted laser desorption/ionization (MALDI) imaging (IMS) following middle cerebral artery occlusion (MCAO) reperfusion injury in the mouse. IMS is a powerful method to not only discriminate Gangliosides by their oligosaccharide components, but also by their carbon length within their sphingosine base. Mice were subjected to a 30 min unilateral MCAO followed by long-term survival (up to 28 days of reperfusion). Brain sections were sprayed with the matrix 5-Chloro-2-mercaptobenzothiazole, scanned and analyzed for a series of Ganglioside molecules using an Applied Biosystems 4800 MALDI TOF/TOF. Traditional histological and immunofluorescence techniques were performed to assess brain tissue damage and verification of the expression of Gangliosides of interest. Results revealed a unique anatomical profile of GM1, GD1 and GT1b (d18∶1, d20∶1 as well as other members of the glycosphingolipid family). There was marked variability in the ratio of expression between ipsilateral and contralateral cortices for the various detected Ganglioside species following MCAO-reperfusion injury. Most interestingly, MCAO resulted in the transient induction of both GM2 and GM3 signals within the ipsilateral hemisphere; at the border of the infarcted tissue. Taken together, the data suggest that brain region specific expression of Gangliosides, particularly with respect to hydrocarbon length, may play a role in neuronal responses to injury.
Ana Rodriguez - One of the best experts on this subject based on the ideXlab platform.
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Anti-Ganglioside antibodies in patients with Zika virus infection-associated Guillain-Barré Syndrome in Brazil
PLoS neglected tropical diseases, 2019Co-Authors: Juan Rivera-correa, Isadora Cristina De Siqueira, Sabrina G. R. Mota, Mateus Santana Do Rosário, Pedro Antônio Pereira De Jesus, Luiz Carlos Junior Alcantara, Joel D. Ernst, Ana RodriguezAbstract:Zika virus infection is associated with the development of Guillain-Barre syndrome (GBS), a neurological autoimmune disorder caused by immune recognition of Gangliosides and other components at nerve membranes. Using a high-throughput ELISA, we have analyzed the anti-glycolipid antibody profile, including Gangliosides, of plasma samples from patients with Zika infections associated or not with GBS in Salvador, Brazil. We have observed that Zika patients that develop GBS present higher levels of anti-Ganglioside antibodies when compared to Zika patients without GBS. We also observed that a broad repertoire of Gangliosides was targeted by both IgM and IgG anti-self antibodies in these patients. Since Zika virus infects neurons, which contain membrane Gangliosides, antigen presentation of these infected cells may trigger the observed autoimmune anti-Ganglioside antibodies suggesting direct infection-induced autoantibodies as a cause leading to GBS development. Collectively, our results establish a link between anti-Ganglioside antibodies and Zika-associated GBS in patients.
Nobuhiro Yuki - One of the best experts on this subject based on the ideXlab platform.
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molecular mimicry between Gangliosides and lipopolysaccharides of campylobacter jejuni isolated from patients with guillain barre syndrome and miller fisher syndrome
The Journal of Infectious Diseases, 1997Co-Authors: Nobuhiro YukiAbstract:Some patients developed Guillain-Barre syndrome (GBS) after being given bovine Gangliosides. Patients with GBS subsequent to Campylobacter jejuni enteritis frequently have IgG antibody to GM 1 Ganglioside. Miller Fisher syndrome (MFS), a variant of GBS, is associated with IgG antibody to GQ 1b Ganglioside. The existence of molecular mimicry between GM 1 and lipopolysaccharide of C. jejuni isolated from a GBS patient and that between GQ 1b and C. jejuni lipopolysaccharides from patients with MFS are shown herein. The molecular mimicry between infectious agents and Gangliosides may function in the production of anti-Ganglioside antibodies and the development of GBS and MFS.
Jin-ichi Inokuchi - One of the best experts on this subject based on the ideXlab platform.
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altered expression of Ganglioside gm3 molecular species and a potential regulatory role during myoblast differentiation
Journal of Biological Chemistry, 2017Co-Authors: Lucas Veillon, Sandro Sonnino, Maria Grazia Ciampa, Laura Mauri, Chihiro Sato, Ken Kitajima, Alessandro Prinetti, Jin-ichi InokuchiAbstract:Gangliosides (sialic acid-containing glycosphingolipids) help regulate many important biological processes, including cell proliferation, signal transduction, and differentiation, via formation of functional microdomains in plasma membranes. The structural diversity of Gangliosides arises from both the ceramide moiety and glycan portion. Recently, differing molecular species of a given Ganglioside are suggested to have distinct biological properties and regulate specific and distinct biological events. Elucidation of the function of each molecular species is important and will provide new insights into Ganglioside biology. Gangliosides are also suggested to be involved in skeletal muscle differentiation; however, the differential roles of Ganglioside molecular species remain unclear. Here we describe striking changes in quantity and quality of Gangliosides (particularly GM3) during differentiation of mouse C2C12 myoblast cells and key roles played by distinct GM3 molecular species at each step of the process.
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GM3 and diabetes
Glycoconjugate Journal, 2014Co-Authors: Jin-ichi InokuchiAbstract:We demonstrated the molecular pathogenesis of type 2 diabetes and insulin resistance focusing on the interaction between insulin receptor and GM3 Ganglioside in adipocytes and propose a working hypothesis “metabolic disorders, such as type 2 diabetes, are membrane microdomain disorders caused by aberrant expression of Gangliosides”. It is expected that the development of novel diagnosis of metabolic syndrome by identifying the specific Ganglioside species and a therapeutic strategy “membrane microdomain ortho-signaling therapy”.
