食欲素信号传导的化学与生物学
Chemistry and biology of orexin signaling.
作者信息
Kodadek Thomas, Cai Di
机构信息
Departments of Chemistry and Cancer Biology, The Scripps Research Institute, Scripps Florida, Jupiter, FL 33458, USA.
出版信息
Mol Biosyst. 2010 Aug;6(8):1366-75. doi: 10.1039/c003468a. Epub 2010 Jun 7.
Abstract
The orexins are neurohormones that, in concert with their cognate receptors, regulate a number of important physiological processes, including feeding, sleep, reward seeking and energy homeostasis. The orexin receptors have recently emerged as important drug targets. This review provides an overview of recent development in deciphering the biology of orexin signaling as well as efforts to manipulate orexin signaling pharmacologically.
摘要
食欲素是一种神经激素，它与其同源受体协同作用，调节许多重要的生理过程，包括进食、睡眠、寻求奖励和能量平衡。食欲素受体最近已成为重要的药物靶点。这篇综述概述了在解读食欲素信号生物学方面的最新进展以及在药理学上操纵食欲素信号的研究成果。
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本文引用的文献
1
Discovery Of An Orexin Receptor Positive Potentiator.一种食欲素受体阳性增强剂的发现。
Chem Sci. 2010 Jul;1(1). doi: 10.1039/C0SC00197J.
2
Orexin-1 receptor co-localizes with pancreatic hormones in islet cells and modulates the outcome of streptozotocin-induced diabetes mellitus.食欲素 1 受体在胰岛细胞中与胰腺激素共存，并调节链脲佐菌素诱导的糖尿病的结果。
PLoS One. 2010 Jan 6;5(1):e8587. doi: 10.1371/journal.pone.0008587.
3
A key role for orexin in panic anxiety.食欲素在惊恐焦虑中的关键作用。
Nat Med. 2010 Jan;16(1):111-5. doi: 10.1038/nm.2075. Epub 2009 Dec 27.
4
Amyloid-beta dynamics are regulated by orexin and the sleep-wake cycle.淀粉样蛋白β的动态变化受食欲素和睡眠-觉醒周期的调节。
Science. 2009 Nov 13;326(5955):1005-7. doi: 10.1126/science.1180962. Epub 2009 Sep 24.
5
Understanding the Warburg effect: the metabolic requirements of cell proliferation.理解瓦伯格效应：细胞增殖的代谢需求。
Science. 2009 May 22;324(5930):1029-33. doi: 10.1126/science.1160809.
6
Enhanced orexin receptor-2 signaling prevents diet-induced obesity and improves leptin sensitivity.增强的食欲素受体-2信号传导可预防饮食诱导的肥胖并提高瘦素敏感性。
Cell Metab. 2009 Jan 7;9(1):64-76. doi: 10.1016/j.cmet.2008.10.010.
7
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Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19480-5. doi: 10.1073/pnas.0808023105. Epub 2008 Nov 24.
8
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Bioorg Med Chem Lett. 2008 Nov 1;18(21):5729-33. doi: 10.1016/j.bmcl.2008.09.079. Epub 2008 Sep 26.
9
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Proc Natl Acad Sci U S A. 2008 Sep 16;105(37):14070-5. doi: 10.1073/pnas.0806993105. Epub 2008 Sep 8.
10
Orexin receptor antagonists: medicinal chemistry and therapeutic potential.食欲素受体拮抗剂：药物化学与治疗潜力
Curr Top Med Chem. 2008;8(11):977-87. doi: 10.2174/156802608784936746.
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