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多巴胺:功能、信号传递与神经疾病的关联。

Dopamine: Functions, Signaling, and Association with Neurological Diseases.

机构信息

Laboratory of Chemical Neuroanatomy, Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, 05508-000, Brazil.

Center for Translational Neuroscience, Sanford Burnham Prebys (SBP) Medical Discovery Institute, 10901 North Torrey Pines Rd., La Jolla, CA, 92037, USA.

出版信息

Cell Mol Neurobiol. 2019 Jan;39(1):31-59. doi: 10.1007/s10571-018-0632-3. Epub 2018 Nov 16.

Abstract

The dopaminergic system plays important roles in neuromodulation, such as motor control, motivation, reward, cognitive function, maternal, and reproductive behaviors. Dopamine is a neurotransmitter, synthesized in both central nervous system and the periphery, that exerts its actions upon binding to G protein-coupled receptors. Dopamine receptors are widely expressed in the body and function in both the peripheral and the central nervous systems. Dopaminergic signaling pathways are crucial to the maintenance of physiological processes and an unbalanced activity may lead to dysfunctions that are related to neurodegenerative diseases. Unveiling the neurobiology and the molecular mechanisms that underlie these illnesses may contribute to the development of new therapies that could promote a better quality of life for patients worldwide. In this review, we summarize the aspects of dopamine as a catecholaminergic neurotransmitter and discuss dopamine signaling pathways elicited through dopamine receptor activation in normal brain function. Furthermore, we describe the potential involvement of these signaling pathways in evoking the onset and progression of some diseases in the nervous system, such as Parkinson's, Schizophrenia, Huntington's, Attention Deficit and Hyperactivity Disorder, and Addiction. A brief description of new dopaminergic drugs recently approved and under development treatments for these ailments is also provided.

摘要

多巴胺能系统在神经调节中发挥重要作用,例如运动控制、动机、奖励、认知功能、母婴和生殖行为。多巴胺是一种神经递质,在中枢神经系统和外周组织中合成,通过与 G 蛋白偶联受体结合发挥作用。多巴胺受体广泛表达于全身,在中枢和外周神经系统中均有功能。多巴胺能信号通路对维持生理过程至关重要,其活性失衡可能导致与神经退行性疾病相关的功能障碍。揭示这些疾病的神经生物学和分子机制可能有助于开发新的治疗方法,为全球患者提高生活质量。在这篇综述中,我们总结了多巴胺作为儿茶酚胺类神经递质的作用,并讨论了通过多巴胺受体激活在正常大脑功能中引发的多巴胺信号通路。此外,我们描述了这些信号通路在引发一些神经系统疾病(如帕金森病、精神分裂症、亨廷顿病、注意缺陷多动障碍和成瘾)的发生和进展中的潜在作用。还简要介绍了最近批准和正在开发的用于治疗这些疾病的新型多巴胺能药物。

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