Glutamate decarboxylase 2 (GAD65) (GAD65)

Glutamate decarboxylase 2 (GAD65) is a 65 kDa enzyme that catalyzes the conversion of L-glutamate into gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the vertebrate central nervous system (UniProt P18089). While it plays a vital role in neurotransmission, GAD65 is also expressed in the insulin-producing beta cells of the pancreas and serves as a primary autoantigen in the pathogenesis of Type 1 Diabetes (T1D) (PubMed: 33531304). In T1D, the immune system mistakenly identifies GAD65 as foreign, leading to T-cell mediated destruction of beta cells. Therapeutic strategies targeting GAD65, such as the Diamyd vaccine, involve the administration of recombinant human GAD65 to induce immune tolerance and prevent further beta-cell loss (ClinicalTrials.gov: NCT03893422). Additionally, high titers of GAD65 autoantibodies are associated with rare neurological disorders like Stiff-Person Syndrome, where they interfere with GABAergic signaling (StatPearls: NBK537305). Understanding GAD65 is crucial for developing precision immunotherapies aimed at modulating the immune response in autoimmune conditions.

Other names

GAD265 kDa glutamic acid decarboxylaseGlutamate decarboxylase 65 kDa isoformGlutamate decarboxylase-2

Antigen-specific immunotherapy designed to induce immune tolerance and regulatory T-cell responses to preserve pancreatic beta-cell function (PubMed: 33531304).