Title:GABA-transaminase: A Key Player and Potential Therapeutic Target for
Neurological Disorders
Volume: 24
Issue: 1
Author(s): Sania Grover, Raj Kumar Narang and Shamsher Singh*
Affiliation:
- Department of Pharmacology, ISF College of Pharmacy (An Autonomous College), Moga-142001, Punjab, India
Keywords:
GABA, GABA-T, epilepsy, autism, huntington's disease, multiple sclerosis, alzheimer's disease.
Abstract: Neurological disorders such as epilepsy, autism, Huntington's disease, multiple sclerosis,
and Alzheimer's disease alter brain functions like cognition, mood, movements, and language, severely
compromising the well-being of persons, suffering from their negative effects. The neurotransmitters
(GABA, glutamate, norepinephrine, dopamine) are found to be involved in neuronal
signaling and neurotransmission. GABA, a "commanding neurotransmitter" is directly or indirectly
associated with various neurological disorders. GABA is metabolized to succinic semialdehyde by a
mitochondrial gamma-aminobutyric acid-transaminase (GABA-T) enzyme. Therefore, the alterations
in the GABA performance in the distinct regions of the brain via GABA-T overstimulation or inhibition
would play a vital role in the pathogenesis of various neurological disorders. This review emphasizes
the leading participation of GABA-T in neurological disorders like Huntington's disease,
epilepsy, autism, Alzheimer's disease, and multiple sclerosis. In Huntington's disease, epilepsy, and
multiple sclerosis, the surfeited performance of GABA-T results in diminished levels of GABA,
whereas in autism, the subsidence of GABA-T activity causes the elevation in GABA contents,
which is responsible for behavioral changes in these disorders. Therefore, GABA-T inhibitors (in
Huntington's disease, epilepsy, and multiple sclerosis) or agonists (in autism) can be used therapeutically.
In the context of Alzheimer's disease, some researchers favor the stimulation of GABA-T activity
whereas some disagree with it. Therefore, the activity of GABA-T concerning Alzheimer's
disease is still unclear. In this way, studies of GABA-T enzymatic activity in contrast to neurological
disorders could be undertaken to understand and be considered a therapeutic target for several
GABA-ergic CNS diseases.