GABA-转氨酶:神经系统疾病的关键角色和潜在治疗靶点。

Sania Grover, Raj Kumar Narang, Shamsher Singh
{"title":"GABA-转氨酶:神经系统疾病的关键角色和潜在治疗靶点。","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":"{\"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}","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

摘要

癫痫、自闭症、亨廷顿氏病、多发性硬化症和阿尔茨海默病等神经系统疾病会改变大脑的认知、情绪、运动和语言等功能,严重影响患者的身心健康。神经递质(GABA、谷氨酸、去甲肾上腺素、多巴胺)被发现参与神经元信号传递和神经传递。GABA 是一种 "指令性神经递质",直接或间接地与各种神经系统疾病有关。GABA 通过线粒体中的γ-氨基丁酸转氨酶(GABA-T)代谢为琥珀酸半醛。因此,通过 GABA-T 过度刺激或抑制而改变大脑不同区域的 GABA 性能,将在各种神经系统疾病的发病机制中发挥重要作用。这篇综述强调了 GABA-T 在亨廷顿氏病、癫痫、自闭症、阿尔茨海默病和多发性硬化症等神经系统疾病中的主要参与作用。在亨廷顿氏病、癫痫和多发性硬化症中,GABA-T 的过度活跃导致 GABA 含量降低,而在自闭症中,GABA-T 活性的减弱导致 GABA 含量升高,从而引起这些疾病的行为变化。因此,GABA-T 抑制剂(亨廷顿氏病、癫痫和多发性硬化症)或激动剂(自闭症)可用于治疗。在阿尔茨海默病方面,一些研究人员赞成刺激 GABA-T 的活性,而另一些研究人员则持不同意见。因此,GABA-T 在阿尔茨海默病方面的活性尚不明确。因此,可以开展 GABA-T 酶活性与神经系统疾病的对比研究,以了解并将其视为多种 GABA 能中枢神经系统疾病的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
GABA-transaminase: A Key Player and Potential Therapeutic Target for Neurological Disorders.

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.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信