Roles of metabotropic glutamate receptor 8 in neuropsychiatric and neurological disorders.
Roles of metabotropic glutamate receptor 8 in neuropsychiatric and neurological disorders.
复制标题
DOI：
10.1016/bs.irn.2022.10.003
复制
发表时间：
2023
影响因子：
--
通讯作者：
Wang, John Q
中科院分区：
文献类型：
--
作者：
Mao, Li-Min;Mathur, Nirav;Shah, Karina;Wang, John Q
代谢型谷氨酸（mGlu）受体是G蛋白偶联受体。在八种mGlu亚型（mGlu 1 -8）中，mGlu 8越来越受到关注。该亚型定位于神经递质释放的突触前活性区，并且是对谷氨酸具有高亲和力的mGlu亚型之一。作为一种G i/o偶联的自身受体，mGlu 8抑制谷氨酸释放以维持谷氨酸能传递的稳态。mGlu 8受体在边缘脑区域中表达，并且在调节动机、情感、认知和运动功能中起关键作用。新出现的证据强调异常mGlu 8活性的临床相关性增加。使用mGlu 8选择剂和敲除小鼠的研究揭示了mGlu 8受体与多种神经精神和神经系统疾病的联系，包括焦虑症、癫痫、帕金森病、药物成瘾和慢性疼痛。在这些疾病的动物模型中，mGlu 8受体在某些边缘结构中的表达和功能经历了长期的适应性变化，这可能有助于对脑疾病的发病机制和病理学至关重要的神经递质传递的重塑。这篇综述总结了目前对mGlu 8生物学的认识，以及该受体可能参与几种常见的精神和神经系统疾病。
Metabotropic glutamate (mGlu) receptors are G protein-coupled receptors. Among eight mGlu subtypes (mGlu1-8), mGlu8 has drawn increasing attention. This subtype is localized to the presynaptic active zone of neurotransmitter release and is among the mGlu subtypes with high affinity for glutamate. As a Gi/o-coupled autoreceptor, mGlu8 inhibits glutamate release to maintain homeostasis of glutamatergic transmission. mGlu8 receptors are expressed in limbic brain regions and play a pivotal role in modulating motivation, emotion, cognition, and motor functions. Emerging evidence emphasizes the increasing clinical relevance of abnormal mGlu8 activity. Studies using mGlu8 selective agents and knockout mice have revealed the linkage of mGlu8 receptors to multiple neuropsychiatric and neurological disorders, including anxiety, epilepsy, Parkinson’s disease, drug addiction, and chronic pain. Expression and function of mGlu8 receptors in some limbic structures undergo long-lasting adaptive changes in animal models of these disorders, which may contribute to the remodeling of glutamatergic transmission critical for the pathogenesis and symptomatology of brain illnesses. This review summarizes the current understanding of mGlu8 biology and the possible involvement of the receptor in several common psychiatric and neurological disorders.