GABA-transaminase: A Key Player and Potential Therapeutic Target for Neurological Disorders

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.

Cite this article as:

Grover Sania, Narang Kumar Raj and Singh Shamsher*, GABA-transaminase: A Key Player and Potential Therapeutic Target for Neurological Disorders, Central Nervous System Agents in Medicinal Chemistry 2024; 24 (1) . https://dx.doi.org/10.2174/0118715249267700231116053516