Glutamate decarboxylase 2 (GAD2) (GAD2)

Glutamate decarboxylase 2 (GAD2), also known as GAD65, is a critical enzyme that catalyzes the conversion of L-glutamate into gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the central nervous system [1, 11]. Encoded by the GAD2 gene, this 65 kDa isoform is primarily localized to presynaptic terminals and is activated during periods of high demand for GABA, distinguishing it from the GAD67 isoform which maintains basal GABA levels [3, 13]. GAD2 is also expressed in pancreatic beta cells, where it serves as a major autoantigen in the development of Type 1 Diabetes and the rare neurological disorder Stiff-person syndrome [5, 9]. The presence of high-titer GAD65 autoantibodies is a well-established diagnostic biomarker for these conditions [6, 15]. Therapeutic strategies targeting GAD2 include immunotherapies like the Diamyd vaccine, which aims to induce immune tolerance and preserve beta-cell function, as well as gene therapies and small molecule modulators designed to restore GABAergic balance in neurological diseases such as epilepsy and Parkinson's disease [7, 13]. Additionally, GAD2 inhibitors are being explored as research tools to understand the role of GABA in various physiological processes [8].

Other names

GAD6565 kDa glutamic acid decarboxylaseGlutamate decarboxylase 65 kDa isoformGAD-65

Glutamate decarboxylase 2 catalyzes the conversion of L-glutamate to gamma-aminobutyric acid (GABA) [1, 11]. Therapeutic mechanisms include the induction of immune tolerance to the GAD65 autoantigen to preserve pancreatic beta-cell function, the use of gene therapy to restore GABAergic tone in the brain, and the modulation of enzyme expression through epigenetic mechanisms [3, 5, 13].