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痕量胺相关受体1信号转导通路的研究进展

孙萌, 张晨琛, 李继涛, 司天梅, 苏允爱^*

北京大学第六医院，北京大学精神卫生研究所，国家卫生健康委员会精神卫生学重点实验室(北京大学)，国家精神心理疾病临床医学研究中心(北京大学第六医院)，北京 100191

摘要

痕量胺相关受体1 (trace amine-associated receptor 1, TAAR1)是一类经典G蛋白耦联受体，广泛分布于哺乳动物的脑内，尤其是边缘系统和富集单胺能神经元的区域，是一种在所有物种中高度保守的TAAR亚型。TAAR1可以特异性应答中枢神经系统和外周组织中的内源性微量胺，在单胺系统和谷氨酸系统失调引发的精神障碍的病理生理学机制中具有重要意义。另外，TAAR1调节剂可以作用于内向整流钾离子通道，对突触传递和神经元活动具有调节作用。最新的研究表明，TAAR1通过调节细胞内信号通路和底物磷酸化发挥一系列生理功能，与情绪、认知、恐惧和成瘾有着密切的联系。本综述对TAAR1信号转导通路的相关研究进行了详细的梳理，旨在揭示TAAR1作为神经精神疾病药物治疗新靶点的巨大潜力。

关键词： 痕量胺相关受体1; 信号通路; 单胺系统; 谷氨酸系统; 内向整流钾离子通道

Research progress of trace amine-associated receptor 1 signaling pathways

SUN Meng, ZHANG Chen-Chen, LI Ji-Tao, SI Tian-Mei, SU Yun-Ai^*

Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China

Abstract

Trace amine-associated receptor 1 (TAAR1) is a classical type of G-protein-coupled receptor, which is widely distributed in the brain of mammals, especially in the limbic system and the region rich in monoaminergic neurons, and it is a highly conserved TAAR subtype in all species. TAAR1 can specifically respond to endogenous trace amines in the central nervous system and peripheral tissues, and plays an important role in the pathophysiological mechanisms involving the dysregulation of monoamine system and glutamate system leading to mental disorders. In addition, TAAR1 modulator can act on inwardly rectifying potassium channels and regulate synaptic transmission and neuronal activity. According to the latest research findings, TAAR1 exerts a series of functions by regulating signal pathways and substrate phosphorylation, which is related to emotion, cognition, fear and addiction. Therefore, we conducted a detailed review of relevant studies on the TAAR1 signaling pathways, aiming at revealing the great potential of TAAR1 as a new target for drug treatment of neuropsychiatric disorders.

Key words: trace amine-associated receptor 1; signaling pathway; monoamine system; glutamate system; inwardly rectifying potassium channel

收稿日期：　　录用日期：

通讯作者：苏允爱　　E-mail: suyunai@bjmu.edu.cn

DOI: 10.13294/j.aps.2023.0072

引用本文：

孙萌, 张晨琛, 李继涛, 司天梅, 苏允爱. 痕量胺相关受体1信号转导通路的研究进展[J]. 生理学报 2024; 76 (1): 89-96.

SUN Meng, ZHANG Chen-Chen, LI Ji-Tao, SI Tian-Mei, SU Yun-Ai. Research progress of trace amine-associated receptor 1 signaling pathways. Acta Physiol Sin 2024; 76 (1): 89-96 (in Chinese with English abstract).