代谢型谷氨酸受体5（mGluR5）在脆性X综合征发病机制中的作用。
Role for metabotropic glutamate receptor 5 (mGluR5) in the pathogenesis of fragile X syndrome.
作者信息
Dölen Gül, Bear Mark F
机构信息
Howard Hughes Medical Institute, The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
出版信息
J Physiol. 2008 Mar 15;586(6):1503-8. doi: 10.1113/jphysiol.2008.150722. Epub 2008 Jan 17.
Abstract
Metabotropic glutamate receptors (mGluRs) have been implicated in a diverse variety of neuronal functions. Studies reviewed here indicate that exaggerated signalling through mGluR5 can account for multiple cognitive and syndromic features of fragile X syndrome, the most common inherited form of mental retardation and autism. Since a reduction of mGluR5 signalling can reverse fragile X phenotypes, these studies provide a compelling rationale for the use of mGluR5 antagonists for the treatment of fragile X and related disorders.
摘要
代谢型谷氨酸受体（mGluRs）已被证明参与多种神经元功能。此处综述的研究表明，通过mGluR5的过度信号传导可解释脆性X综合征的多种认知和综合征特征，脆性X综合征是最常见的遗传性智力障碍和自闭症形式。由于mGluR5信号传导的减少可逆转脆性X综合征的表型，这些研究为使用mGluR5拮抗剂治疗脆性X综合征及相关疾病提供了令人信服的理论依据。
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2
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ScientificWorldJournal. 2006 Sep 20;6:1164-76. doi: 10.1100/tsw.2006.220.
3
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Science. 2006 Aug 25;313(5790):1093-7. doi: 10.1126/science.1128134.
4
Anisomycin infused into the hippocampus fails to block "reconsolidation" but impairs extinction: the role of re-exposure duration.注入海马体的茴香霉素未能阻断“重新巩固”，但会损害消退：再暴露持续时间的作用。
Learn Mem. 2006 Jan-Feb;13(1):27-34. doi: 10.1101/lm.91206.
5
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J Neurophysiol. 2006 May;95(5):3291-5. doi: 10.1152/jn.01316.2005. Epub 2006 Feb 1.
6
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7
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8
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