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γ-氨基丁酸受体的内吞作用:神经系统中的信号传导

Endocytosis of GABA receptor: Signaling in nervous system.

作者信息

Sharma Preeti, Sharma B Sharan, Raval Hardik, Singh Vijai

机构信息

Shree Vipratech Diagnostics, Dehgam, Gujarat, India.

Rivaara Labs, KD Hospital, Vaishnodevi Circle, Ahmedabad, Gujarat, India.

出版信息

Prog Mol Biol Transl Sci. 2023;196:125-139. doi: 10.1016/bs.pmbts.2022.06.032. Epub 2022 Jul 30.

DOI:10.1016/bs.pmbts.2022.06.032
PMID:36813355
Abstract

GABA (ᵞ-aminobutyric acid), is the principal neurotransmitter known for its inhibitory role in chemical synapses. Being localized primarily in the central nervous system (CNS) it maintains a balance between excitatory (regulated by another neurotransmitter, glutamate) and inhibitory impulses. GABA acts by binding to their specific receptors GABA and GABA when released into the post-synaptic nerve terminal. Both of these receptors are responsible for fast and slow inhibition of neurotransmission, respectively. GABA is a ligand-gated ionopore receptor which opens the Cl ion channel and decreases the resting potential of the membrane resulting into inhibition of the synapse. On the other hand, GABA is a metabotropic receptor which increases the K ion levels preventing Ca ion release inhibiting the release of other neurotransmitters into the presynaptic membrane. The internalization and trafficking of these receptors is also conducted through distinct pathways and mechanism, discussed in detail in the chapter. Without the desired levels of GABA in the body, the psychological and neurological states of brain get hard to maintain. Various neurodegenerative diseases/disorders have been associated to low levels of GABA, such as anxiety, mood disorders, fear, schizophrenia, hungtington's chorea, seizures, epilepsy, etc. The allosteric sites present on GABA receptors have been proved to be potent drug targets to pacify the pathological states of these brain related disorders to an extent. Further in depth studies focussing on the subtypes of GABA receptors and their comprehensive mechanism are required to explore new drug targets and therapeutic avenues for effectual management of GABA related neurological diseases.

摘要

γ-氨基丁酸(GABA)是一种主要的神经递质,以其在化学突触中的抑制作用而闻名。它主要定位于中枢神经系统(CNS),维持兴奋性(由另一种神经递质谷氨酸调节)和抑制性冲动之间的平衡。GABA释放到突触后神经末梢时,通过与特定的GABA受体和GABA受体结合发挥作用。这两种受体分别负责快速和慢速抑制神经传递。GABA是一种配体门控离子通道受体,它打开氯离子通道,降低膜的静息电位,从而抑制突触。另一方面,GABA是一种代谢型受体,它增加钾离子水平,阻止钙离子释放,抑制其他神经递质释放到突触前膜。这些受体的内化和运输也通过不同的途径和机制进行,本章将详细讨论。体内缺乏所需水平的GABA时,大脑的心理和神经状态将难以维持。多种神经退行性疾病/障碍都与GABA水平低有关,如焦虑、情绪障碍、恐惧、精神分裂症、亨廷顿舞蹈病、癫痫发作、癫痫等。GABA受体上的变构位点已被证明是有效的药物靶点,可在一定程度上缓解这些与大脑相关疾病的病理状态。需要进一步深入研究GABA受体的亚型及其全面机制,以探索新的药物靶点和治疗途径,有效管理与GABA相关的神经疾病。

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Endocytosis of GABA receptor: Signaling in nervous system.γ-氨基丁酸受体的内吞作用:神经系统中的信号传导
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