中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (6): 1257-1258.doi: 10.4103/1673-5374.327338

• 观点:神经损伤修复保护与再生 • 上一篇    下一篇

在胺先天嗅觉、情绪和成人神经发生之间交叉点的微量胺相关受体

  

  • 出版日期:2022-06-15 发布日期:2021-12-17

Trace amine-associated receptors at the cross-road between innate olfaction of amines, emotions, and adult neurogenesis

Evgeniya V. Efimova, Nataliia V. Katolikova, Evgeny V. Kanov, Raul R. Gainetdinov*   

  1. Institute of Translational Biomedicine and Saint Petersburg University Hospital, Saint Petersburg State University, Saint Petersburg, Russia
  • Online:2022-06-15 Published:2021-12-17
  • Contact: Raul R. Gainetdinov, MD, PhD, gainetdinov.raul@gmail.com.
  • Supported by:
    The present work was supported by Russian Science Foundation grant 19-75-30008 (to RRG). 

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摘要： Neural Regen Res：靶向微量胺相关受体可治疗各种精神和神经退行性疾病？
微量胺是一类内源性生物胺，在蛋白质分解过程中富集并浓缩在某些体液中。它们主要被认为是氨基酸和单胺代谢的副产物。微量胺相关受体 (TAAR) 是一个由微量胺激活的 G 蛋白偶联受体家族，包括 TAAR1、TAAR2、TAAR5、TAAR6、TAAR8 和 TAAR9。TAAR1 可以调节经典的大脑神经递质系统——多巴胺、血清素和谷氨酸，它们与许多神经精神疾病的发病机制有关。TAAR1 激动剂的临床前研究表明它们有望用于治疗精神分裂症、药物依赖、抑郁症和双相情感障碍。 TAAR1 已经在临床上被证明是一种新的药理靶点。在最新临床试验中，TAAR1 激动剂显示出治疗精神分裂症的巨大希望，其独特的作用机制不涉及 D2 多巴胺受体阻断。所有其他 TAAR 都被认为是专门的嗅觉受体，感知由挥发性胺编码的先天气味，在外周脑中没有显着功能。在嗅觉上皮的感觉神经元及其对肾小球的投射中发现TAAR5在感知与社会相关的先天气味方面很重要。 
来自俄罗斯圣彼得堡国立大学的Raul R. Gainetdinov团队最近证明了“嗅觉”TAAR5 受体存在于大脑边缘区域，可以调节经典的单胺系统、情绪行为和成人神经发生。虽然 TAAR5 在气味检测中的参与得到了很好的描述，但它们在嗅觉系统之外的功能却被忽视了。在嗅觉上皮以外的一些区域存在TAAR5 mRNA，包括杏仁核、下丘脑腹内侧和脊髓。由于缺乏选择性配体，对TAAR5功能的研究受到限制。已知缺乏TAAR1会影响血清素和多巴胺系统。在TAAR5敲除小鼠中，纹状体和海马中的血清素水平也降低。注射5-HT1A 受体选择性激动剂8-OH-DPAT在突变小鼠中显示出显著的体温变化和多巴胺系统变化。TAAR5敲除小鼠纹状体中多巴胺及其代谢物水平升高了 30%。 因此，TAAR5受体参与脑单胺系统的调节，正如之前针对 TAAR1 受体所显示的那样。不仅 TAAR1 和 TAAR5，而且所有其他 TAAR 受体都可以通过各种机制充当大脑中经典单胺系统的调节剂。
    文章在《中国神经再生研究（英文版）》杂志2022年 6 月  6 期发表。

https://orcid.org/0000-0003-2951-6038 (Raul R. Gainetdinov) 

Abstract: Trace amines are the class of endogenous biogenic amines that traditionally include beta-phenylethylamine, p-tyramine, tryptamine, octopamine, and others. Many trace amines represent products of amino acids decarboxylation by bacterial decarboxylases during tissue putrefaction or by endogenous decarboxylases in the body. Production of trace amines by gut microbiota is also known (Berry et al., 2017; Gainetdinov et al., 2018). Thus, trace amines are enriched during the decomposition of proteins and concentrated in certain bodily fluids. Their physiological action in mammals has been noted a long time ago, however, they were considered mostly as by-products of amino acid and monoamine metabolism. This was changed with the discovery in 2001 of trace amine-associated receptors (TAARs), a family of G protein-coupled receptors that are activated by trace amines. In humans, 6 types of functional TAAR receptors were identified - TAAR1, TAAR2, TAAR5, TAAR6, TAAR8 and TAAR9 (Berry et al., 2017; Gainetdinov et al., 2018). Since then, there is a growing interest in this family of receptors as possible new targets for pharmacotherapy. Indeed, several psychotropic substances have been shown to display high affinity to the most studied of the TAAR receptors - TAAR1, which has notable expression in the brain and some peripheral tissues (Berry et al., 2017). TAAR1 can modulate classical brain neurotransmitter systems - dopamine, serotonin, and glutamate, that are involved in the pathogenesis of many neuropsychiatric disorders. Indeed, the preclinical study of TAAR1 agonists showed them to be promising for the treatment of schizophrenia, drug dependence, depression and bipolar disorder (Berry et al., 2017; Gainetdinov et al., 2018). TAAR1 is already proven clinically as a novel pharmacological target. In clinical trials, TAAR1 agonist showed great promise for the treatment of schizophrenia with a unique mechanism of action not involving D2 dopamine receptor blockade (Koblan et al., 2020). At the same time, all other TAARs have been considered as exclusively olfactory receptors sensing innate odors encoded by volatile amines with no significant function in the brain or the periphery. However, we recently demonstrated that an “olfactory” TAAR5 receptor is present in the limbic brain areas and can regulate classical monoamine systems, emotional behavior, and adult neurogenesis (Espinoza et al., 2020; Efimova et al., 2021).