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膜相关鸟苷酸激酶(MAGUK)蛋白:谷氨酸能突触中药物干预的新靶点。

MAGUK proteins: new targets for pharmacological intervention in the glutamatergic synapse.

作者信息

Gardoni Fabrizio

机构信息

Department of Pharmacological Sciences and Centre of Excellence on Neurodegenerative Diseases, University of Milan, via Balzaretti 9, 20133 Milan, Italy.

出版信息

Eur J Pharmacol. 2008 May 6;585(1):147-52. doi: 10.1016/j.ejphar.2008.01.048. Epub 2008 Feb 26.

Abstract

In the postsynaptic density of excitatory glutamatergic synapses, membrane associated guanylate kinase (MAGUK) proteins, such as Post-Synaptic Density 95 (PSD-95), organize ionotropic glutamate receptors and their associated signalling proteins regulating the strength of synaptic activity. Modifications of MAGUK proteins function in the glutamatergic synapse such as alterations of MAGUK proteins interaction with N-Methyl-D-Aspartate (NMDA) receptors regulatory subunits are common events in several neurodegenerative disorders. Thus, a better knowledge and understanding of MAGUK structure and function as well as of the molecular events regulating MAGUK-mediated interactions in the glutamatergic synapse could lead to the identification of new targets for pharmaceutical intervention for neurodegenerative diseases.

摘要

在兴奋性谷氨酸能突触的突触后致密物中,膜相关鸟苷酸激酶(MAGUK)蛋白,如突触后致密物95(PSD-95),组织离子型谷氨酸受体及其相关信号蛋白,调节突触活动的强度。MAGUK蛋白在谷氨酸能突触中的功能修饰,如MAGUK蛋白与N-甲基-D-天冬氨酸(NMDA)受体调节亚基相互作用的改变,是几种神经退行性疾病中的常见事件。因此,更好地了解和理解MAGUK的结构和功能,以及调节谷氨酸能突触中MAGUK介导的相互作用的分子事件,可能会为神经退行性疾病的药物干预识别新的靶点。

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