The regulation of glutamic acid decarboxylases in GABA neurotransmission in the brain

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter that is required for the control of synaptic excitation/inhibition and neural oscillation. GABA is synthesized by glutamic acid decarboxylases (GADs) that are widely distributed and localized to axon terminals of inhibitory neurons as well as to the soma and, to a lesser extent, dendrites. The expression and activity of GADs is highly correlated with GABA levels and subsequent GABAergic neurotransmission at the inhibitory synapse. Dysregulation of GADs has been implicated in various neurological disorders including epilepsy and schizophrenia. Two isoforms of GADs, GAD67 and GAD65, are expressed from separate genes and have different regulatory processes and molecular properties. This review focuses on the recent advances in understanding the structure of GAD, its transcriptional regulation and post-transcriptional modifications in the central nervous system. This may provide insights into the pathological mechanisms underlying neurological diseases that are associated with GAD dysfunction.