{"title":"GABA-transaminase: A Key Player and Potential Therapeutic Target for Neurological Disorders.","authors":"Sania Grover, Raj Kumar Narang, Shamsher Singh","doi":"10.2174/0118715249267700231116053516","DOIUrl":null,"url":null,"abstract":"<p><p>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 <i>via</i> 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.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":"57-67"},"PeriodicalIF":0.0000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Central nervous system agents in medicinal chemistry","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/0118715249267700231116053516","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
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.