Glutamate decarboxylase 1 and 2 (GAD65/67)

Glutamate decarboxylase 65 and 67 (GAD65/67) are the two primary isoforms of the enzyme responsible for the synthesis of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system [1, 2]. GAD67, encoded by the GAD1 gene, is constitutively active and maintains basal GABA levels throughout the cytoplasm, while GAD65, encoded by the GAD2 gene, is localized to synaptic vesicles and provides activity-dependent GABA synthesis during peak neurotransmission [1, 3]. Beyond the brain, these enzymes are also expressed in pancreatic beta cells, where GABA acts as a paracrine signaling molecule [4, 11]. GAD65 is a significant clinical target due to its role as a major autoantigen in Type 1 diabetes and rare neurological conditions like Stiff-person syndrome [2, 13]. Therapeutic interventions include GAD65-based vaccines designed to induce immune tolerance in diabetic patients and gene therapies that deliver GAD genes to specific brain regions to restore inhibitory balance in Parkinson's disease [2, 15].

Other names

GAD1GAD2Glutamate decarboxylase 65Glutamate decarboxylase 67Glutamic acid decarboxylaseGAD65GAD67

Enzyme activation, Immunomodulation (immune tolerance induction), Gene therapy-mediated enzyme expression