Metabotropic Glutamate Receptors in Central Nervous System Diseases
Metabotropic Glutamate Receptors in Central Nervous System Diseases
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DOI：
10.2174/1389450116666150316224011
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发表时间：
2016-01-01
影响因子：
3.2
通讯作者：
Cryan, John F.
中科院分区：
文献类型：
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作者：
Golubeva, Anna V.;Moloney, Rachel D.;Cryan, John F.
过去30年的广泛研究表明，代谢型谷氨酸（mGlu）受体在中枢神经系统（CNS）的主要功能中起着至关重要的作用。大量的临床前研究提供了证据，表明mGlu受体的药理学靶向可以有效地减轻动物模型中许多CNS疾病的症状发展和进展。在这篇综述中，我们总结了目前的知识mGlu受体参与神经精神疾病（精神分裂症，抑郁症，焦虑和认知障碍，疼痛感知和成瘾）的病理生理学，以及神经退行性疾病（阿尔茨海默氏症，亨廷顿氏病和帕金森氏病）和神经发育（脆性X综合征和自闭症谱系障碍）疾病。我们进一步强调了mGlu受体的药理学调节剂在这些疾病中的治疗潜力，描述了这些化合物的临床试验结果，并讨论了翻译困难的潜在来源。
Extensive research over the past thirty years has demonstrated a vital role for metabotropic glutamate (mGlu) receptors in the major functions of the central nervous system (CNS). A wealth of preclinical studies provide evidence that pharmacological targeting of mGlu receptors can effectively attenuate the development of symptoms and progression of many CNS disorders in animal models. In this review we summarize the current knowledge on the involvement of mGlu receptors in the pathophysiology of neuropsychiatric disorders (schizophrenia, depression, anxiety and cognitive disorders, pain perception and addiction), as well as neurodegenerative (Alzheimer's, Huntington's and Parkinson's diseases) and neurodevelopmental (fragile X syndrome and autism spectrum disorders) diseases. We further emphasize the therapeutic potential of mGlu receptors' pharmacological modulators in these diseases, describe the results of clinical trials with these compounds and discuss the potential sources of translational difficulties.