Metabotropic glutamate receptors as targets for multipotential treatment of neurological disorders.
Metabotropic glutamate receptors as targets for multipotential treatment of neurological disorders.
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DOI：
10.1016/j.nurt.2008.10.038
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发表时间：
2009-01
期刊：
影响因子：
--
通讯作者：
Faden AI
中科院分区：
文献类型：
--
作者：
Byrnes KR;Loane DJ;Faden AI
谷氨酸是中枢神经系统（CNS）中的主要兴奋性神经递质，其参与许多细胞功能，包括细胞死亡和存活。代谢型谷氨酸受体（mGluR）是G蛋白偶联受体，根据信号转导途径和药理学特征分为三组。组I、II和III mGluR存在于CNS内和外周的细胞类型上，包括神经元、小胶质细胞、星形胶质细胞、少突胶质细胞、T和B淋巴细胞、成骨细胞、肝细胞和内皮细胞等。这些受体对细胞有许多影响，可以影响创伤后的结果，包括减少神经元和寡神经胶质细胞死亡、炎症和内皮通透性。因此，mGluRs是一种有前途的多潜能治疗方法。由于CNS创伤和神经变性的病理学是多因素的，包括氧化应激、线粒体分解、炎症等，因此用于调节多个病理生理学途径的疗法可能证明比针对单个靶点的疗法更有效。本文综述了mGluR调节在急性和慢性损伤和神经退行性变中的多潜能治疗效用。
Glutamate is a major excitatory neurotransmitter in the central nervous system (CNS) that is involved in numerous cellular functions, including cell death and survival. Metabotropic glutamate receptors (mGluR) are G-protein coupled receptors that have been divided into three groups on the basis of signal transduction pathways and pharmacological profiles. Group I, II and III mGluRs are found on cell types within and peripheral to the CNS, including neurons, microglia, astrocytes, oligodendrocytes, T and B lymphocytes, osteoblasts, hepatocytes and endothelial cells, among others. These receptors have a number of effects on cells that can affect outcome after trauma, including reducing neuronal and olidogendroglial cell death, inflammation, and endothelial permeability. Therefore, mGluRs are a promising multipotential therapeutic approach. As the pathology of CNS trauma and neurodegeneration is multi-factorial, including oxidative stress, mitochondrial breakdown, inflammation and so on, therapies that serve to modulate multiple pathophysiological pathways may prove more effective than those directed at a single target. This review examines the multipotential therapeutic utility of mGluR modulation in acute and chronic injury and neurodegeneration.
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