Pancreatic beta-cells and gamma-aminobutyric acid (GABA)-secreting neurons both express the enzyme glutamic acid decarboxylase (GAD) which is a major target of autoantibodies associated with beta-cell destruction and impairment of GABA-ergic neurotransmitter pathways. The predominant form of GAD in pancreatic beta-cells, GAD65, is synthesized as a soluble hydrophilic molecule, which is modified...

-Aminobutyric acid type A receptors (GABAARs) are the major sites of fast inhibitory neurotransmission in the brain, and the numbers of these receptors at the cell surface can determine the strength of GABAergic neurotransmission. Chronic changes in neuronal activity lead to an adaptive modulation in the efficacy of GABAergic synaptic inhibition, brought about in part by changes in the number o...

Stiff person syndrome (SPS) is a highly-disabling neurological disorder of the CNS characterized by progressive muscular rigidity and spasms. In approximately 60-80% of patients there are autoantibodies to glutamic acid decarboxylase (GAD), the enzyme that synthesizes gamma-amino butyric acid (GABA), the predominant inhibitory neurotransmitter of the CNS. Although GAD is intracellular, it is th...

A utoimmune diabetes in the popular nonobese diabetic (NOD) mouse results from a T-cell– mediated destruction of the insulin-producing -cells (1) and serves as a model for human type 1 diabetes (2,3). The mechanisms that initiate early peri-islet inflammation and the destructive components that arise later specifically targeting -cells occur naturally in NOD mice (2,3). Two obstacles hinder our...

Master Degree Student, Laboratory of Panic & Respiration, Institute of Psychiatry, Federal University of Rio de Janeiro, INCT Translational Medicine, Rio de Janeiro RJ, Brazil; Assistant Professor, Neurology Service, State of Rio de Janeiro University, Rio de Janeiro RJ, Brazil; Assistant Professor, Federal University of State of Rio de Janeiro, Rio de Janeiro RJ, Brazil; Associate Professor. L...

BACKGROUND Prediction, risk assessment, and diagnosis of autoimmune diseases often rely on detection of autoantibodies directed to multiple target antigens, such as the 65-kDa isoform of glutamic acid decarboxylase (GAD65-abs) and the tyrosine phosphatase-like protein islet antigen-2 (IA2-abs), the two major subspecificities of islet cell antibodies (ICAs) associated with insulin-dependent diab...

Glutamic acid decarboxylase is responsible for synthesizing GABA, the major inhibitory neurotransmitter, and exists in two isoforms--GAD65 and GAD67. The enzyme is cleaved under excitotoxic conditions, but the mechanisms involved and the functional consequences are not fully elucidated. We found that excitotoxic stimulation of cultured hippocampal neurons with glutamate leads to a time-dependen...

In this issue of Diabetes, Cervin et al. (1) investigated whether patients with latent autoimmune diabetes in adults (LADA) (defined as age at diabetes onset 35 years, GADA positive), analyzing known risk alleles for type 1 and type 2 diabetes, share genetic polymorphisms with type 1 diabetes (age at onset 35 years) and/or type 2 diabetes (age at onset 35 years, GADA negative). In their LADA pa...

Reelin and glutamic acid decarboxylase (GAD)67 expressed by cortical gamma-aminobutyric acid-ergic interneurons are down-regulated in schizophrenia. Because epidemiological studies of schizophrenia fail to support candidate gene haploinsufficiency of Mendelian origin, we hypothesize that epigenetic mechanisms (i.e., cytosine hypermethylation of CpG islands present in the promoter of these genes...