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AMPA 受体组成和转运在突触可塑性和疾病中的作用。

The Role of AMPARs Composition and Trafficking in Synaptic Plasticity and Diseases.

机构信息

Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.

State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.

出版信息

Cell Mol Neurobiol. 2022 Nov;42(8):2489-2504. doi: 10.1007/s10571-021-01141-z. Epub 2021 Aug 26.

Abstract

AMPA receptors are tetrameric ionic glutamate receptors, which mediate 90% fast excitatory synaptic transmission induced by excitatory glutamate in the mammalian central nervous system through the activation or inactivation of ion channels. The alternation of synaptic AMPA receptor number and subtype is thought to be one of the primary mechanisms that involve in synaptic plasticity regulation and affect the functions in learning, memory, and cognition. The increasing of surface AMPARs enhances synaptic strength during long-term potentiation, whereas the decreasing of AMPARs weakens synaptic strength during the long-term depression. It is closely related to the AMPA receptor as well as its subunits assembly, trafficking, and degradation. The dysfunction of any step in these precise regulatory processes is likely to induce the disorder of synaptic transmission and loss of neurons, or even cause neuropsychiatric diseases ultimately. Therefore, it is useful to understand how AMPARs regulate synaptic plasticity and its role in related neuropsychiatric diseases via comprehending architecture and trafficking of the receptors. Here, we reviewed the progress in structure, expression, trafficking, and relationship with synaptic plasticity of AMPA receptor, especially in anxiety, depression, neurodegenerative disorders, and cerebral ischemia.

摘要

AMPA 受体是四聚体离子型谷氨酸受体,通过离子通道的激活或失活,介导哺乳动物中枢神经系统中 90%由兴奋性谷氨酸诱导的快速兴奋性突触传递。突触 AMPA 受体数量和亚型的交替被认为是参与突触可塑性调节的主要机制之一,影响学习、记忆和认知功能。在长时程增强过程中,表面 AMPAR 的增加增强了突触强度,而在长时程抑制过程中,AMPAR 的减少减弱了突触强度。这与 AMPA 受体及其亚基的组装、运输和降解密切相关。这些精确调节过程中任何步骤的功能障碍都可能导致突触传递紊乱和神经元丧失,甚至最终导致神经精神疾病。因此,通过理解受体的结构和运输,了解 AMPAR 如何调节突触可塑性及其在相关神经精神疾病中的作用是很有帮助的。在这里,我们综述了 AMPA 受体的结构、表达、运输及其与突触可塑性的关系的研究进展,特别是在焦虑、抑郁、神经退行性疾病和脑缺血方面的进展。

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