Prieto G Aleph
Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
J Cent Nerv Syst Dis. 2017 Aug 16;9:1179573517726335. doi: 10.1177/1179573517726335. eCollection 2017.
Dopamine D receptors (DR) modulate neuronal activity in several brain regions including cortex, striatum, cerebellum, and hippocampus. A growing body of evidence suggests that aberrant DR signaling contributes to multiple brain diseases, such as Parkinson's disease, essential tremor, schizophrenia, and addiction. In line with these findings, DR has emerged as a potential target in the treatment of neurological disorders. However, the mechanisms underlying neuronal DR signaling are poorly understood, either in healthy or diseased brain. Here, I review the molecular mechanisms involved in DR signaling via monomeric DR and heteromeric receptor complexes (e.g., DR-DR, DR-DR, DR-AR, and DR-Dnf). I focus on DR signaling pathways that, according to recent reports, contribute to pathological brain states. In particular, I describe evidence on both quantitative (e.g., increased number or affinity) and qualitative (e.g., switched signaling) changes in DR that has been associated with brain dysfunction. I conclude with a description of basic mechanisms that modulate DR signaling such as desensitization, as disruption of these mechanisms may underlie pathological changes in DR signaling. Because several lines of evidence support the idea that imbalances in DR signaling alter neural function, a better understanding of downstream DR pathways is likely to reveal novel therapeutic strategies toward dopamine-related brain disorders.
多巴胺 D 受体（DR）调节包括皮层、纹状体、小脑和海马体在内的多个脑区的神经元活动。越来越多的证据表明，异常的 DR 信号传导与多种脑部疾病有关，如帕金森病、特发性震颤、精神分裂症和成瘾。与这些发现一致，DR 已成为治疗神经系统疾病的一个潜在靶点。然而，无论是在健康大脑还是患病大脑中，神经元 DR 信号传导的潜在机制都知之甚少。在此，我综述了通过单体 DR 和异聚体受体复合物（如 DR-DR、DR-DR、DR-AR 和 DR-Dnf）进行 DR 信号传导所涉及的分子机制。我关注的是根据最近的报道，导致病理性脑状态的 DR 信号通路。特别是，我描述了与脑功能障碍相关的 DR 在数量（如数量增加或亲和力增加）和质量（如信号转换）方面变化的证据。我最后描述了调节 DR 信号传导的基本机制，如脱敏，因为这些机制的破坏可能是 DR 信号传导病理变化的基础。由于有几条证据支持 DR 信号传导失衡会改变神经功能这一观点，更好地理解 DR 下游通路可能会揭示针对多巴胺相关脑部疾病的新治疗策略。
