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PubMed1998

Long-term ethanol consumption selectively impairs ganglioside pathway in rat brain.

Gangliosides are sialo-glycosphingolipids that play important roles in the interaction of cells with their environment and are thus involved in the regulation of many cellular events. Sialic acid residues are important for the conformation of a glycomolecule, their structural stability and their functions. Although decreased brain ganglioside sialic acid has been previously reported as a result of chronic ethanol treatment in rats, no reports are available on the sialylation of specific gangliosides and/or the mechanism leading to depletion of their sialic acid residues. Therefore, in this investigation, we have examined the effects of chronic ethanol treatment on (1) incorporation of [4,5-3H]N-acetylmannosamine (ManNAc) into specific rat brain gangliosides, GD3, GD1a, GT1a, and GT1b; and (2) enzymatic activities of brain sialyltransferase and sialidase at specific subcellular levels. The experiments were done in male Wistar rats pair-fed with either ethanol or control liquid diets for a period of 8 weeks. The rats were intracerebroventricularly injected with labeled ManNAc (30 microCi/rat) and killed after 90 min. Radioactivity was determined in respective ganglioside bands separated on a thin layer chromatography system. Specific activities of sialyltransferase and sialidase were assessed using GM3 and GD3 as substrates, respectively. The results showed significant decreases of 57.7% (p < 0.001) and 68.9% (p < 0.001), respectively, in the labeled ManNAc incorporation into GD3 and GD1a fractions in rats of the ethanol group, compared with rats of the control group. No significant changes were noted in the incorporation of labeled ManNAc into GT1a or GT1b ganglioside fractions between the ethanol and control groups. Concomitantly, compared with control rats, a decrease of 18.9% (p < 0.05), 20.6% (p < 0.05), and 15.8% (p < 0.001) was found in the sialyltransferase activity, respectively, at the whole brain, and brain Golgi and synaptosomal levels. However, dramatic increases of 32.4% (p < 0.05), 105% (p < 0.001), and 150% (p < 0.001) in sialidase activity were found, respectively, at the whole brain and brain cytosol and synaptosomal fractions of rat treated chronically with ethanol. Thus, we conclude that the deleterious actions of ethanol on the sialylation of rat brain gangliosides is specific, and the reduced sialic acid label found in GD3 and GD1a in this study is mainly due to increased activity of brain sialidase. Furthermore, the study reaffirms our tenet that, regardless of whether it is the liver or the brain, glycosylation cascade is one of the main target of the deleterious attacks of ethanol.

Alcoholism↗
PubMed1998

Photochemical labeling of HL-60 cell membrane proteins with radioiodinated, 4-azidosalicylic acid acylated derivatives of gangliosides.

To detect HL-60 human promyelocytic leukemia cell proteins involved in the uptake of gangliosides from the culture medium we used photoreactive, 4-azidosalicylic acid (ASA) acylated and radioiodinated (200 Ci/mmole) derivatives of GM3, GD3, GM1, and FucGM1 gangliosides. Gangliosides-ASA, added to the medium at 15-20 nM concentration, followed a similar time course of uptake. After 1 min incubation cell bound gangliosides-ASA could not be removed with trypsin, but only 5-10% remained after incubation with BSA. The proportion of cell bound gangliosides-ASA resistant to BSA treatment increased with time of incubation up to 76% after 20 h. As shown on TLC, GM3- and GD3-ASA were catabolized to LacSph-ASA and ceramide-ASA, while GM1-ASA was hydrolyzed to GM2-ASA. FucGM1-ASA was converted to GM1-ASA very slowly. Upon irradiation with UV lamp, cell bound gangliosides-ASA crosslinked to and photolabeled many proteins but the distribution of radioactivity after SDS/PAGE was very uneven and did not correlate with Coomassie staining. In all experiments the 42 kDa protein bands were most intensely photolabeled. Photolabeling of 42 kDa proteins decreased with time of incubation as compared to lower molecular mass pro teins. With all gangliosides-ASA used similar but not identical protein photolabeling patterns were obtained. Photolabeling patterns with GM3- and GD3-ASA differed from those with GM1- and FucGM1-ASA.

Azides↗
PubMed1998

L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol stimulates ganglioside biosynthesis, neurite outgrowth and synapse formation in cultured cortical neurons, and ameliorates memory deficits in ischemic rats.

To address the role of brain gangliosides in synaptic plasticity, the synthetic ceramide analog, 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) was used to manipulate the biosynthesis of gangliosides in cultured cortical neurons. Spontaneous synchronized oscillatory activity of intracellular Ca2+ between the neurons, which represents synapse formation, was suppressed by the depletion of endogenous gangliosides by D-threo-PDMP, an inhibitor of glucosylceramide synthase. The decreased functional synapse formation was normalized by supplementation of GQ1b but not by the other gangliosides, suggesting that de novo synthesis of ganglioside GQ1b is essential for the synaptic activity (Mizutani A. et al., Biochem. Biophys. Res. Commun. 222, 494-498, 1996). On the other hand, the enantiomer of the inhibitor, L-threo-PDMP, could elevate cellular levels of glycosphingolipids including gangliosides. This paper presents our recent findings on the neurotrophic actions of L-threo-PDMP in vitro and in vivo. We found that L-PDMP could up-regulate neurite outgrowth, functional synapse formation and ganglioside biosynthesis through activating GM3, GD3 and GQ1b synthases. Simultaneously, the activity of p42 mitogen-activated protein kinase was also facilitated by L-PDMP. To evaluate the efficacy of this drug on long term memory, rats were trained for 2 weeks using an 8-arm radial maze task, and then forebrain ischemia was induced by 4-vessel occlusion (for 10 min x 2 with a 60 min interval). Repeated treatment of L-threo-PDMP (40 mg/kg, i.p. for 6 days, twice a day) starting 24 h after the ischemia, improved the deficit of the well-learned spatial memory, demonstrating the potential therapeutic use of the ceramide analog for treatment of neurodegenerative disorders.

Animals↗
PubMed1998

Chemical, metabolic and immunological characterization of gangliosides of human glioma cells.

The patterns of ganglioside profiles were studied in 10 human glioma and one melanoma cell lines. Ganglio-series gangliosides, GM3 (NeuAc alpha2-3Gal beta1-4Glc beta1-Cer) and GM2 (GalNAc beta 1-4 (NeuAc alpha2-3)Gal beta1-4Glc beta 1-1Cer), and a neolacto-series ganglioside, sialylparagloboside (SPG) (NeuAc alpha 2-3Gal beta1-4GlcNAc beta1-3Gal beta1-4Glc beta1-1Cer), were the predominant constituents. The activities of the two key enzymes, GM3 synthetase and lactotriaosyl ceramide (Lc3Cer) synthetase, alone did not account for the ganglioside profile. Metabolic labeling with the use of [3H]glucosamine-HCl showed more pronounced difference in the synthetic rate of each ganglioside type, in which GM2 was the most strongly labeled in 7 out of the 10 glioma cell lines. On quantifying the chemical content of GM3 and GM2, the GM3/GM2 molar ratio of above 2.0 was arbitrarily classified into GM3 dominant type (KG-1C and Mewo); the ratio below 0.5 was designated as GM2 dominant type (H4, U138MG, U373MG, T98G and A172); and the ratio between 0.5 and 2.0 was regarded as GM3 and GM2-co-dominant type (U87MG, Hs683, SW1088 and U118MG). Subsequently, the capabilities of the antibody binding to these gangliosides were examined in native forms in the cell membrane and in chemically-isolated forms. The intensity of reaction against chemically isolated GM3 and GM2 gangliosides was dependent on the quantity, and GM2 was more reactive than GM3; however, the reactivities on the cell surface did not correlate with the chemical content indicating other factors to influence their immunoreactivities.

Antibodies, Monoclonal↗
PubMed1992

Metabolism of GM1 ganglioside in cultured skin fibroblasts: anomalies in gangliosidoses, sialidoses, and sphingolipid activator protein (SAP, saposin) 1 and prosaposin deficient disorders.

Cultured skin fibroblasts from controls and patients with lysosomal storage diseases were loaded with GM1 ganglioside that had been labelled with tritium in its ceramide moiety. After a 65-h or 240-h incubation, a large percentage of this ganglioside remained undegraded in GM1 gangliosidoses, whereas in the other storage diseases studied, one of its metabolites accumulated by 2-4 fold relative to controls. Labelled GM2 ganglioside accumulated in 4 variants of GM2 gangliosidosis, whereas labelled GM3 ganglioside accumulated in sialidosis, galactosialidoses and sphingolipid activator protein 1 (SAP-1, saposin B) and prosaposin (saposin A, B, C and D) deficient lipidoses. The reduced degradation of GM3 ganglioside in the SAP-1 and prosaposin deficiencies was attributed to the deficient function of SAP-1. The prosaposin deficient cells also showed a reduced re-utilization of radioactive metabolites from GM1 ganglioside (i.e. sphingosine and fatty acid) for phospholipid biosynthesis compared with fibroblasts from the SAP-1 deficient patient or normal controls. This anomaly was ascribed to the previously shown defect in ceramide degradation in prosaposin deficiency.

Child, Preschool↗
PubMed2002

Detection of anti-ganglioside antibodies in Guillain-Barré syndrome and its variants by the agglutination assay.

Sera from 40 patients with Guillain-Barré syndrome (GBS), including the subtypes acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), acute motor and sensory axonal neuropathy (AMSAN), and Miller Fisher syndrome (MFS) were examined for the presence of anti-ganglioside antibodies using the ganglioside agglutination assay, and the enzyme-linked immunosorbent assay (ELISA). In the ELISA system, sera were tested for IgM and IgG antibodies to GM1, GM2, GD1a, GD1b, GT1b, and GQ1b gangliosides. Antibodies to gangliosides were detected in 21 (53%) of the GBS patients by agglutination assay and in 17 (43%) of the patients by ELISA. Some of the sera reacted with more than one ganglioside. Antibodies were not found in the control sera that were studied. The agglutination assay may be useful for rapid screening of GBS sera for antibodies to multiple gangliosides.

Agglutination Tests↗
PubMed1985

Detection of a tumour-associated ganglioside in plasma of patients with neuroblastoma.

An abnormal circulating ganglioside was found in patients with neuroblastoma. This ganglioside appeared as a single band by resorcinol-HCl staining of thin-layer chromatograms of purified total gangliosides isolated from as little as 1 ml of patient plasma. It is a major ganglioside of neuroblastoma tumour tissue and was present (250-1500 pmol lipid-bound sialic acid/ml) in the plasma of five patients with widespread neuroblastoma. In contrast, the ganglioside was not detected (less than 50 pmol/ml) in plasma samples of six patients in complete remission, nor in plasma samples of seventeen healthy children and adults. Measurement of this circulating tumour-associated ganglioside should be clinically useful in neuroblastoma, offering a new approach to the detection of tumour and the evaluation of therapy.

Adolescent↗
PubMed2003

The adhesion protein TAG-1 has a ganglioside environment in the sphingolipid-enriched membrane domains of neuronal cells in culture.

We studied the interactions between gangliosides and proteins at the exoplasmic surface of the sphingolipid-enriched membrane domains by ganglioside photolabeling combined with cell surface biotin labeling. After cell photolabeling with radioactive photoactivable derivatives of GM3, GM1 and GD1b gangliosides, followed by cell surface biotin labeling, sphingolipid-enriched domains were prepared and immunoprecipitated with streptavidin-coupled beads, under experimental conditions preserving the integrity of the lipid domain. About 50% of the total radioactivity linked to proteins was associated with acylated tubulin, about 10% with a 135-kDa protein present as a series of species with pI ranging from 6.5 to 8.0, about 5% with a protein of about 70 kDa and with pI near to 6.5. By immunoprecipitation with streptavidin-coupled beads under conditions disrupting the integrity of the lipid domain, the 135 kDa protein was recovered in the immunoprecipitate, that did not contain tubulin. Thus, the 135 kDa protein has an exoplasmic domain, and it was then identified as the GPI-anchored neural cell adhesion molecule TAG-1. Remarkably, TAG-1 was cross-linked in a similar extent by the photoactivated ganglioside GM3, GM1 and GD1b. The three gangliosides bear different oligosaccharide chains, suggesting that the ganglioside/TAG-1 interaction is not specifically associated with the ganglioside oligosaccharide structure.

Animals↗
PubMed1990

Precursor-product relationship between GM1 and GD1a biosynthesized from exogenous GM2 ganglioside in rat liver.

The demonstration of a precursor-product relationship in the course of GM1 and GD1a biosynthesis is described in the present paper. We injected rats with GM2 gangliosides [GalNAc beta 1----4(NeuAc alpha 2----3)Gal beta 1----4Glc beta 1----1'Cer] of brain origin, which were isotopically radiolabeled on the GalNAc ([GalNAc-3H]GM2) or sphingosine ([Sph-3H]GM2) residue. We then compared the time-courses of GM1 and GD1a biosynthesis in the liver after the administration of each radiolabeled GM2 derivative. After the administration of [GalNAc-3H]GM2, GM1, and GD1a were both present as doublets, that could be easily resolved on TLC. The lower spot of each doublet was identified as a species having the typical rat brain ceramide moiety and represented gangliosides formed through direct glycosylation of the injected GM2. The upper spot of each doublet was identified as a species having the typical rat liver ceramide moiety and represented gangliosides formed through recycling of the [3H]GalNAc residue, released during ganglioside catabolism. After the administration of [Sph-3H]GM2, only ganglioside with the rat brain ceramide moiety were found, that represented the sum of ganglioside formed through direct glycosylation and those formed through recycling of some sphingosine-containing fragments. In each case, the time-course of GM1 and GD1a biosynthesis exhibited a precursor-product relationship. The curve obtained from the direct glycosylation showed a timing delay with respect to those obtained from recycling of GM2 fragments. These results are consistent with the hypothesis that the sequential addition of activated sugars to a sphingolipid precursor is a dissociative process, catalyzed by physically independent enzymatic activities.

Animals↗
PubMed1989

Ganglioside composition of astrocytes.

Short-term and long-term (greater than 7 months) cultured astrocytes from 14-day-old rat brain were analyzed for ganglioside content. Analysis of the extracted gangliosides by HPTLC revealed that ganglioside GM1 was absent in 35 days and 235 days cultured astrocytes, and that the predominant ganglioside was GM3, showing a double band in both cases. A small amount of the disialogangliosides (GD3, GD1a) was also detected. More than 70% of radioactivities into ganglioside fractions by cultured astrocytes, in the presence of N-[3H]-acetylmannosamine, appeared in ganglioside GM3. The upper band component of GM3 increased 60% in long-term astrocyte cultures compared to 35-day-old cultures. Also, an increased GD3 content in long-term astrocyte cultures was detected. These results suggest that the increase of GD3 and upper band GM3 in long-term cultured astrocytes might be related to the appearance of small processes showing strong reactivity against GFAP and vimentin during astrocyte-subculture.

Animals↗
PubMed2005

a-Series gangliosides mediate the effects of advanced glycation end products on pericyte and mesangial cell proliferation: a common mediator for retinal and renal microangiopathy?

Advanced glycation end products (AGEs) are involved in the development of microvascular complications, including alterations of retinal pericyte and renal mesangial cell growth occurring during diabetic retinopathy and diabetic nephropathy, respectively. Because gangliosides are implicated in the regulation of cell proliferation, we hypothesized that AGEs could exert cellular effects in part by modulating ganglioside levels. Results of the present study indicate that AGEs caused an inhibition of both bovine retinal pericyte (BRP) and rat renal mesangial cell (RMC) proliferation, associated with an increase of a-series gangliosides consecutive to GM3 synthase activity increase and GD3 synthase activity inhibition. Similar modifications were also found in the renal cortex of diabetic db/db mice compared with controls. Treatment of BRP and RMC with exogenous a-series gangliosides decreased proliferation and blockade of a-series gangliosides with specific antibodies partially protecting the two cell types from the AGE-induced proliferation decrease. Further, inhibition of GM3 synthase using specific SiRNA partially reversed the AGE effects on mesangial cell proliferation. These results suggest that a-series gangliosides are mediators of the adverse AGE effects on BRP and RMC proliferation. They also raise the hypothesis of common mechanisms involved in the development of diabetic retinopathy and diabetic nephropathy.

Animals↗
PubMed1984

Ganglioside-mediated modulation of cell growth, growth factor binding, and receptor phosphorylation.

Glycosphingolipids added exogenously in cell culture are slowly incorporated into plasma membranes, inhibit cell growth, and modify growth behavior ( Laine , R. A., and Hakomori, S. (1973) Biochem. Biophys. Res. Commun. 54, 1039-1045; Keenan , T. W., Schmid, E., Franke , W. W., and Wiegandt , H. (1975) Exp. Cell Res. 92, 259-270). With the availability of purified growth factors and serum-free culture conditions in recent years, we have been able to examine this phenomenon in mouse Swiss 3T3 cells in greater detail with the following results. 1) Cell growth (cell number increase) in serum-free medium was specifically inhibited by the presence of GM1 and to a lesser extent by GM3, but not by NeuAcnLc4 , although the gangliosides were incorporated equally well into cell membranes. GM3 inhibited both platelet-derived growth factor (PDGF)- and epidermal growth factor-stimulated mitogenesis determined by thymidine incorporation, while GM1 could only inhibit PDGF-stimulated mitogenesis. NeuAcnLc4 had no effect on mitogen-stimulated thymidine incorporation. 2) The concentration-dependent binding of 125I-PDGF binding to cells indicated that cells whose growth was inhibited by GM1 or GM3 showed an increased affinity for PDGF as compared to cells grown without addition of ganglioside, while the total number of receptors stayed the same. Addition of ganglioside did not affect the binding of 125I-EGF. 3) No direct interaction was observed between gangliosides and growth factors as evidenced by the lack of competition by ganglioside-containing liposomes for cellular binding of 125I growth factors. 4) GM1 and GM3, but neither NeuAcnLc4 nor Gb4 , inhibited the PDGF-stimulated tyrosine phosphorylation by membrane preparations of a 170,000 molecular weight protein, which is probably the PDGF receptor. Thus, the level of gangliosides GM1 and GM3 in membranes may modulate PDGF receptor function by affecting the degree of tyrosine phosphorylation and may alter the affinity of the receptor for PDGF.

Animals↗
PubMed1976

GM1-ganglioside and lactosylceramide beta-galactosidase from rabbit brain: inhibitor and substrate competition studies.

A rabbit brain beta-galactosidase catalyzes the hydrolysis of synthetic substrates and the natural substrates Gm1-ganglioside, lactosylceramide, and asialo-Gm1-ganglioside. gamma-D-Galactonolactone competitively inhibited hydrolysis of Gm1-ganglioside, lactosylceramide, and MU-galactoside with Ki values of 0.26 mM, 0.13 mM, and 0.77 mM, respectively. From activity plots comparing the degree of inhibition to the inhibitor concentration, a single binding site for each substrate was found. NP-Galactoside inhibited the hydrolysis of Gm1-ganglioside and lactosylceramide, where as Gm1-ganglioside inhibited lactosylceramide hydrolysis. At low substrate concentrations (less than 1 mM), Gm1-ganglioside was hydrolyzed effectively in the presence of NP-galactoside, but at higher concentrations hydrolysis of the latter was preferred. Chloromercuriphenylsulfonic acid and iodoacetate were effective inhibitors of the enzyme, but N-ethylmaleimide was not. The degree of inhibition with chloromercuriphenylsulfonic acid was different for each substrate. At 0.5 mugM chloromercuriphenylsulfonic acid, all activity towards NP-galactoside, 75% towards lactosylceramide, and 25% of the Gm1-ganglioside activity was lost. Two possible models are presented to explain these results. The data favour the presence of multiple active sites in the enzyme.

Animals↗
PubMed1991

Lysosomal and plasma membrane ganglioside GM3 sialidases of cultured human fibroblasts. Differentiation by detergents and inhibitors.

Cultured human fibroblasts contain two sialidases that degrade gangliosides such as GM3: a lysosomal activity that appears identical with the activity towards water-soluble substrates and that is deficient in the genetic lysosomal disorder sialidosis, and another enzyme that seems localized on the external surface of the plasma membrane. In this report we show that both enzymes can be differentiated in the presence of each other by choice of the detergent used for activation, and also by the inhibitory action of some polyanionic compounds such as sulphated glycosaminoglycans. The lysosomal ganglioside GM3 sialidase is greatly stimulated by sodium glycodeoxycholate and, to lesser degrees, by sodium glycocholate and sodium cholate. The ganglioside GM3 sialidase of the plasma membrane is not measurably active under the conditions of the lysosomal enzyme but is specifically activated by the non-ionic detergent Triton X-100. The glycodeoxycholate-stimulated, but not the Triton-activated, ganglioside GM3 sialidase activity was profoundly diminished in cell lines from patients with the lysosomal disorders sialidosis and galactosialidosis; however, both activities were normal in fibroblasts from patients with mucolipidosis IV, previously thought to be a ganglioside sialidase deficiency disorder. Both the lysosomal and the plasma membrane ganglioside GM3 sialidases were inhibited by sialic acids, suramin, dextran sulphate and sulphated glycosaminoglycans. Among the latter, heparin and heparan sulphate showed a much higher inhibitory potency towards the plasma membrane ganglioside GM3 sialidase than towards the lysosomal onw.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbohydrate Metabolism, Inborn Errors↗
PubMed1996

Gangliosides in human uveal melanoma metastatic process.

The inability of current therapy to prevent metastases arising from uveal melanoma often results in patient mortality. With the goal of developing a treatment for metastasis, gangliosides were studied as potential tumor-associated antigens. Our report describes the production of a metastatic liver variant (MH) from a human uveal melanoma cell line (SP6.5). Cells were injected into nude mouse spleens and liver metastases collected 2 months later. After 21 days of in vitro subculture, the cells were re-injected into normal nude mice spleen; 10 cycles (MH10) were performed. Gangliosides were extracted, purified, chromatographed on HPTLC plates and sprayed with a resorcinol-HCl reagent, the sialic acid spots being quantified by densitometry. Gangliosides were analyzed in each metastatic liver variant and compared with the SP6.5 s.c. tumor. The results showed a significant increase in GM3 and a significant decrease in GD3 and GD2 in the last metastatic variants obtained (MH5, MH8, MH9 and MH1O) compared with the primary s.c. tumor, SP6.5. Such evolution in the ganglioside pattern was maintained throughout the progression of the different liver variants. Our results indicate that precursor ganglioside GM3 and gangliosides GD3 and GD2 could be associated with neoplastic evolution of malignancy of human uveal melanoma in nude mice.

Animals↗
PubMed2005

Changes in the neuromuscular synapse induced by an antibody against gangliosides.

In this study, we used a monoclonal IgM antibody from a patient with a pure motor chronic demyelinating polyneuropathy, which binds specifically to the complex gangliosides GM(2), GalNAc-GD(1a), and GalNAc-GM(1b), which appear to have a common epitope of -[GalNAcbeta1-4Gal(3-2alphaNeuAc)beta1]. This was done for the following reasons: (1) to localize these gangliosides in specific cellular components of the neuromuscular junction (NMJ), and (2) to describe the anti-ganglioside antibody-induced structural and functional changes in the NMJs to gain insight into the role of gangliosides in the synaptic function. Using immunofluorescence techniques, we found that these gangliosides are located only in the presynaptic component of the motor end-plates, both in nerve terminals and in Schwann cells. After 2 weeks of continued passive transfer of the IgM monoclonal antibody over the mouse levator auris longus muscle, electromyography showed an axonal or NMJ disorder. Morphology showed important nerve terminal growth and retraction changes. Using intracellular recording electrophysiology, we found neurotransmitter release alterations, including quantal content reduction and an immature expression of voltage-dependent calcium channels similar to what occurred during NMJ development and regeneration. These changes were complement independent. The results showed that these gangliosides were involved in the reciprocal Schwann cell-nerve terminal interactions, including structural stability and neurotransmission.

Animals↗
PubMed1989

Patterns of serum IgM antibodies to GM1 and GD1a gangliosides in amyotrophic lateral sclerosis.

We studied the incidence and clinical correlates of serum antibodies to GM1 and GD1a gangliosides in patients with classical amyotrophic lateral sclerosis (ALS) and other "motor nerve" syndromes. Serum antibodies to GM1 and GD1a gangliosides were measured using enzyme-linked immunosorbent assays. Our results showed that polyclonal immunoglobulin M (IgM) antibodies to the GM1 or GD1a ganglioside or both were present at serum dilutions of 1:25 to 1:4,000 in 78% (57/73) of patients with ALS. Only 8% of normal controls had similar antibodies. The pattern of serum antibody reactivity correlated with the pattern of clinical involvement in our patients. Selective reactivity to GD1a ganglioside was common when upper motor neuron signs were prominent. IgM reactivity to GM1 ganglioside was common in ALS patients with prominent lower motor neuron signs. Most patients with motor neuropathies had serum reactivity to both GM1 and GD1a gangliosides. These results provide further evidence of ongoing autoimmune processes in ALS patients. There is a strong relationship between serum antiganglioside antibodies and patterns of clinical involvement in ALS.

Adult↗
PubMed1989

Immunosuppressive activity of human neuroblastoma tumor gangliosides.

Gangliosides are shed in substantial amounts by some tumors, including human neuroblastoma, and these molecules modulate experimental tumor formation in vivo. We now demonstrate that neuroblastoma tumor gangliosides have potent immunoregulatory activity. Gangliosides of every one of 17 tumors studied were highly inhibitory for the normal in vitro human lymphoproliferative responses to the soluble antigen, tetanus toxoid; 30 nmol ganglioside/ml caused 43% to greater than 99% inhibition and the mean concentration causing 50% inhibition was only 17.3 nmol/ml. Furthermore, gangliosides isolated from clinically more aggressive tumors (Stage III or IV) were up to twice as immunosuppressive as those of the generally less aggressive tumors (Stage I or II) (p less than 0.05). Taken together with the lack of immunosuppressive activity of normal plasma gangliosides, the potent activity of neuroblastoma gangliosides supports the hypothesis that one mechanism by which these shed molecules may act to enhance tumor formation in vivo is through abrogation of the host cellular immune response at the site of tumor formation.

G(M3) Ganglioside↗