Microglia and Glutamate

Q4 Immunology and Microbiology

Advances in Neuroimmune Biology Pub Date : 2013-01-01 DOI:10.3233/NIB-130057

H. Takeuchi

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引用次数: 2

Abstract

Accumulation of activated microglia around degenerative neurons is a common pathological observation in a variety of neurologic disorders. Activated microglia release a large amount of glutamate that induces neurodegeneration in numerous neurologic diseases such as ischemia, inflammation, epilepsy, and neurodegenerative diseases. Although both blockade of glutamate receptors and inhibition of microglial activation are the therapeutic candidates for activated microglia-mediated neurodegenerative diseases, clinical trials have been failed because of adverse effects presumably stemming from disrupted physiological glutamate signaling and suppressed neuroprotective microglial functions. Recent studies revealed that activated microglia specifically produce glutamate using glutaminase and release glutamate via cell-surface gap junction hemichannels. Blockade of microglial hemichannel successfully suppressed disease progression in animal models of brain ischemia, chronic neuropathic pain, multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease. Therefore, hemichannel blockers may offer a promising therapy for various neurologic disorders without causing the above-mentioned adverse effects.

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小胶质细胞和谷氨酸

活化的小胶质细胞在退行性神经元周围积聚是多种神经系统疾病的常见病理观察。激活的小胶质细胞释放大量谷氨酸，在许多神经疾病如缺血、炎症、癫痫和神经退行性疾病中诱导神经变性。尽管阻断谷氨酸受体和抑制小胶质细胞活化都是活化的小胶质细胞介导的神经退行性疾病的治疗候选药物，但临床试验失败的原因可能是生理谷氨酸信号被破坏和神经保护性小胶质细胞功能被抑制。最近的研究表明，激活的小胶质细胞利用谷氨酰胺酶特异性地产生谷氨酸，并通过细胞表面间隙连接半通道释放谷氨酸。在脑缺血、慢性神经性疼痛、多发性硬化症、肌萎缩侧索硬化症和阿尔茨海默病的动物模型中，阻断小胶质半通道成功地抑制了疾病的进展。因此，半通道阻滞剂可能为各种神经系统疾病提供有希望的治疗方法，而不会引起上述不良反应。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Advances in Neuroimmune Biology Immunology and Microbiology-Immunology

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