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痕量胺相关受体1(TAAR1):神经退行性、神经发育性和神经创伤性疾病的新兴治疗靶点。

Trace amine-associated receptor 1 (TAAR1): an emerging therapeutic target for neurodegenerative, neurodevelopmental, and neurotraumatic disorders.

作者信息

Dalvi Saher, Bhatt Lokesh Kumar

机构信息

Department of Pharmacology, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Vile Parle (W), Mumbai, India.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2025 May;398(5):5057-5075. doi: 10.1007/s00210-024-03757-6. Epub 2024 Dec 30.

DOI:10.1007/s00210-024-03757-6
PMID:39738834
Abstract

Trace amines are physiologically active amines present in all organisms. They are structurally identical to traditional monoamines and are rapidly metabolized by monoamine oxidases. The mammalian neurological system generates these molecules at rates equivalent to traditional monoamines, but because of their short half-life, they are only observable in trace quantities. Their receptors are G protein-coupled receptors present in both the CNS and peripheral locations, with trace amine-associated receptor 1 (TAAR1) being the most researched. TAAR1's capacity to regulate glutamatergic and monoaminergic neurotransmission has made it a viable therapeutic target for neuropsychiatric illnesses. Although the TAAR1 role in schizophrenia and other neuropsychiatric disorders is well established, its role in the pathology of neurodegenerative and neurotraumatic disorders recently got attention. This review discusses the role of TAAR1 in neurodegenerative, neurodevelopment, and neurotraumatic disorders and explores its potential to be a novel therapeutic target in these disorders.

摘要

痕量胺是存在于所有生物体中的生理活性胺。它们在结构上与传统单胺相同,并被单胺氧化酶迅速代谢。哺乳动物神经系统产生这些分子的速率与传统单胺相当,但由于它们的半衰期短,只能以痕量观察到。它们的受体是存在于中枢神经系统和外周部位的G蛋白偶联受体,其中痕量胺相关受体1(TAAR1)是研究最多的。TAAR1调节谷氨酸能和单胺能神经传递的能力使其成为神经精神疾病的一个可行治疗靶点。尽管TAAR1在精神分裂症和其他神经精神疾病中的作用已得到充分证实,但其在神经退行性疾病和神经创伤性疾病病理中的作用最近受到了关注。这篇综述讨论了TAAR1在神经退行性疾病、神经发育和神经创伤性疾病中的作用,并探讨了其成为这些疾病新型治疗靶点的潜力。

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Trace amine-associated receptor 1 (TAAR1): an emerging therapeutic target for neurodegenerative, neurodevelopmental, and neurotraumatic disorders.痕量胺相关受体1(TAAR1):神经退行性、神经发育性和神经创伤性疾病的新兴治疗靶点。
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本文引用的文献

1
TAAR1 and 5-HT receptor agonists attenuate autism-like irritability and aggression in rats prenatally exposed to valproic acid.TAAR1和5-羟色胺受体激动剂可减轻产前暴露于丙戊酸的大鼠的自闭症样易怒和攻击性。
Pharmacol Biochem Behav. 2024 Dec;245:173862. doi: 10.1016/j.pbb.2024.173862. Epub 2024 Aug 26.
2
In Vitro Comparison of Ulotaront (SEP-363856) and Ralmitaront (RO6889450): Two TAAR1 Agonist Candidate Antipsychotics.在体比较乌洛他隆(SEP-363856)和瑞美替隆(RO6889450):两种 TAAR1 激动剂候选抗精神病药。
Int J Neuropsychopharmacol. 2023 Sep 25;26(9):599-606. doi: 10.1093/ijnp/pyad049.
3
T1AM/TAAR1 System Reduces Inflammatory Response and β-Amyloid Toxicity in Human Microglial HMC3 Cell Line.
T1AM/TAAR1 系统可减轻人小神经胶质细胞 HMC3 株的炎症反应和 β-淀粉样毒性。
Int J Mol Sci. 2023 Jul 17;24(14):11569. doi: 10.3390/ijms241411569.
4
Ulotaront, a Trace Amine-Associated Receptor 1/Serotonin 5-HT Agonist, in Patients With Parkinson Disease Psychosis: A Pilot Study.乌洛托品,一种痕量胺相关受体1/血清素5-羟色胺激动剂,用于帕金森病精神病患者:一项试点研究。
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Octopamine metabolically reprograms astrocytes to confer neuroprotection against α-synuclein.章鱼胺通过代谢重编程星形胶质细胞来提供对抗α-突触核蛋白的神经保护作用。
Proc Natl Acad Sci U S A. 2023 Apr 25;120(17):e2217396120. doi: 10.1073/pnas.2217396120. Epub 2023 Apr 17.
6
Trace amine-associated receptor 1 (TAAR1) agonism as a new treatment strategy for schizophrenia and related disorders.痕胺相关受体 1(TAAR1)激动剂作为精神分裂症和相关障碍的新治疗策略。
Trends Neurosci. 2023 Jan;46(1):60-74. doi: 10.1016/j.tins.2022.10.010. Epub 2022 Nov 8.
7
Effect of ractopamine on the release of dopamine from the striatum dissected from mice.莱克多巴胺对从小鼠分离出的纹状体中多巴胺释放的影响。
Physiol Int. 2022 Sep 5. doi: 10.1556/2060.2022.00042.
8
Trace Amine Associate Receptor 1 (TAAR1) as a New Target for the Treatment of Cognitive Dysfunction in Alzheimer's Disease.痕量胺相关受体 1(TAAR1)作为治疗阿尔茨海默病认知功能障碍的新靶点。
Int J Mol Sci. 2022 Jul 15;23(14):7811. doi: 10.3390/ijms23147811.
9
Genetic variations in GABA metabolism and epilepsy.γ-氨基丁酸(GABA)代谢的基因变异与癫痫
Seizure. 2022 Oct;101:22-29. doi: 10.1016/j.seizure.2022.07.007. Epub 2022 Jul 15.
10
Excitotoxicity, calcium and mitochondria: a triad in synaptic neurodegeneration.兴奋毒性、钙离子和线粒体:突触神经退行性变的三联体。
Transl Neurodegener. 2022 Jan 25;11(1):3. doi: 10.1186/s40035-021-00278-7.