Basic aspects of GABA-transaminase in neuropsychiatric disorders

Over the last two decades, there have been several studies suggesting the major inhibitory amino acid neurotransmitter gamma-aminobutyric acid (GABA) is involved directly and/or indirectly in the pathogenesis of many neurologic diseases and psychiatric disorders. GABA is mainly degradated to succinic semialdehyde in a reaction catalyzed by the enzyme GABA-transaminase (GABA-T). Inhibition of this enzyme produces considerable elevation of GABA contents in the brain, and such elevation has been found to correlate with pharmacologic and behavioral effects. We focus attention, from the basic aspects, on brain and platelet GABA-T activities in various species, with a special reference to neuropsychiatric disorders. It seems that the activity of GABA-T in the brain and/or in the blood platelets is correlated to certain neuropsychiatric disorders such as alcoholism, epilepsy, and Alzheimer's disease. In animal and human studies, platelet GABA-T was identified with similar kinetic and inhibitor characteristics to those of the brain. Therefore, in this way, studies of the activity of the enzyme GABA-T in relation to neuropsychiatric disorders could be undertaken to understand, diagnose, and treat GABA-related disorders of the central nervous system.