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靶向代谢型谷氨酸受体mGluR4用于治疗中枢神经系统疾病。

Targeting the metabotropic glutamate receptor mGluR4 for the treatment of diseases of the central nervous system.

作者信息

Marino Michael J, Hess J Fred, Liverton Nigel

机构信息

Neuroscience Drug Discovery--Movement Disorders Research, Department of Medicinal Chemistry, Merck Research Laboratories, Merck & Co., PO Box 4, West Point, PA 19486, USA.

出版信息

Curr Top Med Chem. 2005;5(9):885-95. doi: 10.2174/1568026054750263.

Abstract

Over the last several years a great deal of interest has been focused on the metabotropic glutamate receptors as potential targets for the treatment of a variety of disorders of the central nervous system. Recently, selective agonist or allosteric potentiators of mGluR4, one of the group III mGluRs, have been proposed as potential novel therapeutics for the palliative treatment of Parkinson's disease and some forms of epilepsy. mGluR4 stands out amongst the group III mGluRs due to its relatively restricted localization and apparent role in several key neuronal circuits. Work from a number of laboratories has led to the development of more selective tools for the study of mGluR4, as well as refined models of the structure and function of this receptor. In addition, a growing body of literature suggests that mGluR4 plays a key neuroprotective role in broad spectrum of neurodegenerative disorders. It is hoped that this increased understanding of the role of mGluR4 combined with more detailed structural information will spur the development of better pharmacological tools, and ultimately to novel clinical therapy.

摘要

在过去几年中,代谢型谷氨酸受体作为治疗各种中枢神经系统疾病的潜在靶点受到了极大关注。最近,III组代谢型谷氨酸受体之一的mGluR4的选择性激动剂或变构增强剂已被提议作为帕金森病和某些形式癫痫姑息治疗的潜在新型疗法。mGluR4在III组代谢型谷氨酸受体中脱颖而出,因为其定位相对局限,且在几个关键神经回路中具有明显作用。多个实验室的研究工作促成了用于研究mGluR4的更具选择性的工具的开发,以及该受体结构和功能的优化模型。此外,越来越多的文献表明,mGluR4在广泛的神经退行性疾病中发挥关键的神经保护作用。希望对mGluR4作用的深入理解与更详细的结构信息相结合,将推动更好的药理学工具的开发,并最终促成新的临床治疗方法。

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