The Experts below are selected from a list of 177 Experts worldwide ranked by ideXlab platform
David L. Martin - One of the best experts on this subject based on the ideXlab platform.
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Heteromers of Glutamate Decarboxylase isoforms occur in rat cerebellum.
Journal of neurochemistry, 2002Co-Authors: Sabina N. Sheikh, David L. MartinAbstract:The subunit structure of brain Glutamate Decarboxylase in cerebellum was investigated by using gel electrophoresis and antisera that specifically recognize the individual isoforms of brain Glutamate Decarboxylase (termed GAD 65 and GAD 67 ). The antisera were prepared against peptides that corresponded to amino acid sequences specific to each isoform. Each antiserum reacted specifically with the appropriate peptide in an ELISA and with the appropriate form of GAD on immunoblots. Nondenaturing gradient gel electrophoresis indicated that GAD is principally multimeric with monomeric forms comprising
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two isoforms of Glutamate Decarboxylase why
Trends in Pharmacological Sciences, 1998Co-Authors: Jeanjacques Soghomonian, David L. MartinAbstract:Adults express two isoforms of Glutamate Decarboxylase (GAD), GAD67 and GAD65, which are encoded by different independently regulated genes, a situation that differs from that of other neurotransmitters. In this article, J-J. Soghomonian and David Martin review current knowledge on the differences between these two isoforms. Both isoforms are present in most GABA-containing neurones in the CNS, but GAD65 appears to be targeted to membranes and nerve endings, whereas GAD67 is more widely distributed in cells. Both forms can synthesize transmitter GABA, but GAD67 might preferentially synthesize cytoplasmic GABA and GAD65 might preferentially synthesize GABA for vesicular release. Several lines of evidence suggest that the two forms have different roles in the coding of information by GABA-containing neurones.
S. Kamath - One of the best experts on this subject based on the ideXlab platform.
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anti Glutamate Decarboxylase and other antibodies at the onset of childhood iddm a population based study
Diabetologia, 1994Co-Authors: Charles F. Verge, N. J. Howard, Merrill J. Rowley, Ian R. Mackay, Paul Zev Zimmet, M. Egan, H. Hulinska, Ilja Hulinsky, R. A. Silvestrini, S. KamathAbstract:Sera obtained at diagnosis from 273 children (0–14 years) with insulin-dependent diabetes mellitus (IDDM) were studied to compare different autoantibody levels. The subjects comprise 75% of all incident cases in New South Wales, Australia, for a 2-year period (ascertainment >99% complete). Antibodies against Glutamate Decarboxylase were measured by radioimmunoprecipitation, insulin autoantibodies (on 176 sera collected within 4 days of initiation of insulin therapy) by radioimmunoassay, thyroid peroxidase and antigliadin IgA antibodies by enzyme-linked immunoassay, and anti-endomysial IgA and islet cell antibodies by indirect immunofluorescence. Reference ranges for anti-Glutamate Decarboxylase and insulin autoantibodies were determined in a group of non-diabetic children. Of the sera 69% were positive for anti-Glutamate Decarboxylase, 65% for insulin autoantibodies, 71% for islet cell antibodies (⩾20 Juvenile Diabetes Foundation units), 10% for anti-thyroid peroxidase, 2.6% for antigliadin and 3.0% for anti-endomysial antibodies. Islet cell antibodies and insulin autoantibodies were both negative in 13.7% of the sera, while only 5.8% were negative for all three of islet cell antibodies, insulin autoantibodies and anti-Glutamate Decarboxylase. There was a higher frequency of anti-Glutamate Decarboxylase among girls than boys (75% vs 63%, p=0.03) and a negative correlation between the level of insulin autoantibodies and age at diagnosis (r=−0.41, p<0.0001). A higher frequency of antithyroid peroxidase was found with increasing age (p=0.05). Higher titres of islet cell antibodies were associated with a higher frequency of both anti-Glutamate Decarboxylase (p<0.0001) and insulin autoantibodies (p=0.003). Five children (1.8%) with clear elevations of antigliadin and anti-endomysial antibodies were found to have asymptomatic coeliac disease by small bowel biopsy.
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Anti-Glutamate Decarboxylase and other antibodies at the onset of childhood IDDM: a population-based study
Diabetologia, 1994Co-Authors: Charles F. Verge, N. J. Howard, Merrill J. Rowley, Ian R. Mackay, Paul Zev Zimmet, M. Egan, H. Hulinska, Ilja Hulinsky, R. A. Silvestrini, S. KamathAbstract:Sera obtained at diagnosis from 273 children (0–14 years) with insulin-dependent diabetes mellitus (IDDM) were studied to compare different autoantibody levels. The subjects comprise 75% of all incident cases in New South Wales, Australia, for a 2-year period (ascertainment >99% complete). Antibodies against Glutamate Decarboxylase were measured by radioimmunoprecipitation, insulin autoantibodies (on 176 sera collected within 4 days of initiation of insulin therapy) by radioimmunoassay, thyroid peroxidase and antigliadin IgA antibodies by enzyme-linked immunoassay, and anti-endomysial IgA and islet cell antibodies by indirect immunofluorescence. Reference ranges for anti-Glutamate Decarboxylase and insulin autoantibodies were determined in a group of non-diabetic children. Of the sera 69% were positive for anti-Glutamate Decarboxylase, 65% for insulin autoantibodies, 71% for islet cell antibodies (⩾20 Juvenile Diabetes Foundation units), 10% for anti-thyroid peroxidase, 2.6% for antigliadin and 3.0% for anti-endomysial antibodies. Islet cell antibodies and insulin autoantibodies were both negative in 13.7% of the sera, while only 5.8% were negative for all three of islet cell antibodies, insulin autoantibodies and anti-Glutamate Decarboxylase. There was a higher frequency of anti-Glutamate Decarboxylase among girls than boys (75% vs 63%, p=0.03) and a negative correlation between the level of insulin autoantibodies and age at diagnosis (r=−0.41, p
Charles F. Verge - One of the best experts on this subject based on the ideXlab platform.
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anti Glutamate Decarboxylase and other antibodies at the onset of childhood iddm a population based study
Diabetologia, 1994Co-Authors: Charles F. Verge, N. J. Howard, Merrill J. Rowley, Ian R. Mackay, Paul Zev Zimmet, M. Egan, H. Hulinska, Ilja Hulinsky, R. A. Silvestrini, S. KamathAbstract:Sera obtained at diagnosis from 273 children (0–14 years) with insulin-dependent diabetes mellitus (IDDM) were studied to compare different autoantibody levels. The subjects comprise 75% of all incident cases in New South Wales, Australia, for a 2-year period (ascertainment >99% complete). Antibodies against Glutamate Decarboxylase were measured by radioimmunoprecipitation, insulin autoantibodies (on 176 sera collected within 4 days of initiation of insulin therapy) by radioimmunoassay, thyroid peroxidase and antigliadin IgA antibodies by enzyme-linked immunoassay, and anti-endomysial IgA and islet cell antibodies by indirect immunofluorescence. Reference ranges for anti-Glutamate Decarboxylase and insulin autoantibodies were determined in a group of non-diabetic children. Of the sera 69% were positive for anti-Glutamate Decarboxylase, 65% for insulin autoantibodies, 71% for islet cell antibodies (⩾20 Juvenile Diabetes Foundation units), 10% for anti-thyroid peroxidase, 2.6% for antigliadin and 3.0% for anti-endomysial antibodies. Islet cell antibodies and insulin autoantibodies were both negative in 13.7% of the sera, while only 5.8% were negative for all three of islet cell antibodies, insulin autoantibodies and anti-Glutamate Decarboxylase. There was a higher frequency of anti-Glutamate Decarboxylase among girls than boys (75% vs 63%, p=0.03) and a negative correlation between the level of insulin autoantibodies and age at diagnosis (r=−0.41, p<0.0001). A higher frequency of antithyroid peroxidase was found with increasing age (p=0.05). Higher titres of islet cell antibodies were associated with a higher frequency of both anti-Glutamate Decarboxylase (p<0.0001) and insulin autoantibodies (p=0.003). Five children (1.8%) with clear elevations of antigliadin and anti-endomysial antibodies were found to have asymptomatic coeliac disease by small bowel biopsy.
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Anti-Glutamate Decarboxylase and other antibodies at the onset of childhood IDDM: a population-based study
Diabetologia, 1994Co-Authors: Charles F. Verge, N. J. Howard, Merrill J. Rowley, Ian R. Mackay, Paul Zev Zimmet, M. Egan, H. Hulinska, Ilja Hulinsky, R. A. Silvestrini, S. KamathAbstract:Sera obtained at diagnosis from 273 children (0–14 years) with insulin-dependent diabetes mellitus (IDDM) were studied to compare different autoantibody levels. The subjects comprise 75% of all incident cases in New South Wales, Australia, for a 2-year period (ascertainment >99% complete). Antibodies against Glutamate Decarboxylase were measured by radioimmunoprecipitation, insulin autoantibodies (on 176 sera collected within 4 days of initiation of insulin therapy) by radioimmunoassay, thyroid peroxidase and antigliadin IgA antibodies by enzyme-linked immunoassay, and anti-endomysial IgA and islet cell antibodies by indirect immunofluorescence. Reference ranges for anti-Glutamate Decarboxylase and insulin autoantibodies were determined in a group of non-diabetic children. Of the sera 69% were positive for anti-Glutamate Decarboxylase, 65% for insulin autoantibodies, 71% for islet cell antibodies (⩾20 Juvenile Diabetes Foundation units), 10% for anti-thyroid peroxidase, 2.6% for antigliadin and 3.0% for anti-endomysial antibodies. Islet cell antibodies and insulin autoantibodies were both negative in 13.7% of the sera, while only 5.8% were negative for all three of islet cell antibodies, insulin autoantibodies and anti-Glutamate Decarboxylase. There was a higher frequency of anti-Glutamate Decarboxylase among girls than boys (75% vs 63%, p=0.03) and a negative correlation between the level of insulin autoantibodies and age at diagnosis (r=−0.41, p
Toshio Kosaka - One of the best experts on this subject based on the ideXlab platform.
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Synaptic localization of the 67,000 mol. wt isoform of Glutamate Decarboxylase and transmitter function of GABA in the mouse cerebellum lacking the 65,000 mol. wt isoform
Neuroscience, 1999Co-Authors: Kunihiko Obata, Takaichi Fukuda, Shiro Konishi, H. Mitoma, Toshio KosakaAbstract:Subcellular localization of the 67,000 mol. wt isoform of Glutamate Decarboxylase and neurotransmitter function of GABA were investigated in the cerebellum of the mice lacking the 65,000 mol. wt isoform of Glutamate Decarboxylase. The GABA content decreased by 25% in the cerebellum. Putative GABA-releasing terminals from basket/stellate and Golgi cells were immunostained with Glutamate Decarboxylase-67 antibody. Basket cell-derived inhibitory postsynaptic currents in Purkinje cells and the high potassium-induced release of GABA were not significantly affected. Although previous investigations have suggested that Glutamate Decarboxylase-65 is mainly involved in transmitter synthesis and that Glutamate Decarboxylase-67 is transported to the nerve terminals only after association with Glutamate Decarboxylase-65, the present results indicate that Glutamate Decarboxylase-67 is independently concentrated in the nerve terminals and provides GABA for synaptic transmission in the absence of Glutamate Decarboxylase-65.
Hidehiro Mizusawa - One of the best experts on this subject based on the ideXlab platform.
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Disease-specific monoclonal antibodies targeting Glutamate Decarboxylase impair GABAergic neurotransmission and affect motor learning and behavioral functions
Frontiers in Behavioral Neuroscience, 2015Co-Authors: Mario Manto, Rafael Guerra-narbona, Juan Carlos López-ramos, Jerome Honnorat, Yuchio Yanagawa, Christiane S Hampe, Fumihito Saitow, José M. Delgado-garcía, Hidenori Suzuki, Hidehiro MizusawaAbstract:Autoantibodies to the smaller isoform of Glutamate Decarboxylase can be found in patients with type 1 diabetes and a number of neurological disorders, including stiff-person syndrome, cerebellar ataxia and limbic encephalitis. The detection of disease-specific autoantibody epitopes led to the hypothesis that distinct Glutamate Decarboxylase autoantibodies may elicit specific neurological phenotypes. We explored the in vitro/in vivo effects of well-characterized monoclonal Glutamate Decarboxylase antibodies. We found that Glutamate Decarboxylase autoantibodies present in patients with stiff person syndrome (n = 7) and cerebellar ataxia (n = 15) recognized an epitope distinct from that recognized by Glutamate Decarboxylase autoantibodies present in patients with type 1 diabetes mellitus (n = 10) or limbic encephalitis (n = 4). We demonstrated that the administration of a monoclonal Glutamate Decarboxylase antibody representing this epitope specificity (1) disrupted in vitro the association of Glutamate Decarboxylase with γ-Aminobutyric acid containing synaptic vesicles, (2) depressed the inhibitory synaptic transmission in cerebellar slices with a gradual time course and a lasting suppressive effect, (3) significantly decreased conditioned eyelid responses evoked in mice, with no modification of learning curves in the classical eyeblink-conditioning task, (4) markedly impaired the facilitatory effect exerted by the premotor cortex over the motor cortex in a paired-pulse stimulation paradigm, and (5) induced decreased exploratory behavior and impaired locomotor function in rats. These findings support the specific targeting of Glutamate Decarboxylase by its autoantibodies in the pathogenesis of stiff-person syndrome and cerebellar ataxia. Therapies of these disorders based on selective removal of such Glutamate Decarboxylase antibodies could be envisioned.