Orphan GPCRs and neuromodulation.

Orphan GPCRs and neuromodulation.
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DOI:
10.1016/j.neuron.2012.09.009
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发表时间:
2012-10-04
期刊:
影响因子:
16.2
通讯作者:
Civelli O
Civelli O
中科院分区:
医学1区
文献类型:
--
作者:
Civelli O

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大多数 G 蛋白偶联受体 (GPCR) 最初都是孤儿 GPCR。将它们与已知的神经调节剂相匹配,阐明了神经受体家族的广泛多样性。此外,孤儿 GPCR 也已被用作发现新型神经调节剂的靶标。这些发现对我们对大脑功能的理解产生了深远的影响。在这里,我概述了一些新型神经肽如何扩大我们对指导睡眠/觉醒、肥胖发作和进食反应的反应的理解。我还讨论了从孤儿 GPCR 研究中获得的其他进展,例如神经调节的特异性概念或充当传感器而不是突触递质的受体的概念。最后,我认为最近发现的神经调节剂可能是我们理解高级大脑功能和精神疾病的关键。
Most G protein-coupled receptors (GPCRs) started as orphan GPCRs. Matching them to known neuromodulators led to the elucidation of the broad diversity of the neuroreceptor families. Moreover, orphan GPCRs have also been used as targets to discover novel neuromodulators. These discoveries have had profound impact on our understanding of brain function. Here, I present an overview of how some of the novel neuropeptides have enlarged our comprehension of responses that direct sleep/wakefulness, the onset of obesity and the feeding response. I also discuss other advances gained from orphan GPCR studies such as the concept of specificity in neuromodulation or of receptors acting as sensors instead of synaptic transmitters. Finally, I suggest that the recently-discovered neuromodulators may hold the keys to our understanding of higher brain functions and psychiatric disorders.
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