Gamma-aminobutyric acid transporter (GAT) and Gamma-aminobutyric acid transaminase (GABA-T) (GAT and GABA-T)

The gamma-aminobutyric acid transporter (GAT) and gamma-aminobutyric acid transaminase (GABA-T) are two distinct proteins that play central roles in the regulation of GABA, the primary inhibitory neurotransmitter in the central nervous system. GATs are a family of solute carrier proteins (primarily GAT-1, GAT-2, and GAT-3) located on the plasma membranes of neurons and astrocytes, where they facilitate the reuptake of GABA from the synaptic cleft to terminate its inhibitory action. GABA-T, also known as 4-aminobutyrate aminotransferase (ABAT), is a mitochondrial enzyme responsible for the catabolic breakdown of GABA into succinic semialdehyde. Both proteins are major therapeutic targets for increasing GABAergic tone in conditions of neuronal hyperexcitability, such as epilepsy and infantile spasms. Pharmacological inhibition of GAT-1 by drugs like tiagabine increases synaptic GABA availability, while irreversible inhibition of GABA-T by vigabatrin prevents intracellular GABA degradation, leading to elevated neurotransmitter levels. However, therapeutic modulation of these targets is associated with significant safety concerns, including sedation and, in the case of vigabatrin, permanent visual field defects. Ongoing research also explores the role of these targets in other neurological conditions, including anxiety, Huntington's disease, and Alzheimer's disease.

Other names

GABA transporterGABA transaminaseGATGABA-TABAT4-aminobutyrate aminotransferaseSLC6A1SLC6A11SLC6A13SLC6A12GAT-1GAT-2GAT-3BGT-1

Inhibition of GABA reuptake and inhibition of GABA catabolism