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阿尔茨海默病中的 AMPA 受体:病理改变与潜在治疗靶点。

AMPA receptors in Alzheimer disease: Pathological changes and potential therapeutic targets.

机构信息

Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, China.

Laboratory of Neurological Diseases and Brain Function, Institute of Epigenetics and Brain Science, Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.

出版信息

J Neuropathol Exp Neurol. 2024 Nov 1;83(11):895-906. doi: 10.1093/jnen/nlae093.

Abstract

Alzheimer disease (AD) is a prevalent neurodegenerative disorder that affects synapses and leads to progressive cognitive decline. The role of N-methyl-D-aspartic acid (NMDA) receptors in the pathogenesis of AD is well-established as they contribute to excitotoxicity and neurodegeneration in the pathological process of extrasynaptic glutamate concentration. However, the therapeutic potential of the NMDA receptor antagonist memantine in rescuing synaptic damage is limited. Research indicates that α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors also play a significant role in AD. Abnormal transcription, expression, and localization of AMPA receptors lead to synaptic dysfunction and damage, contributing to early cognitive impairment in AD patients. Understanding the impact of AMPA receptors on AD pathogenesis and exploring the potential for the development of AMPA receptor-targeting drugs are crucial. This review aims to consolidate recent research findings on AMPA receptors in AD, elucidate the current state of AMPA receptor research and lay the foundation for future basic research and drug development.

摘要

阿尔茨海默病(AD)是一种常见的神经退行性疾病,影响突触,导致进行性认知能力下降。N-甲基-D-天冬氨酸(NMDA)受体在 AD 的发病机制中起着重要作用,因为它们在突触外谷氨酸浓度的病理过程中导致兴奋性毒性和神经退行性变。然而,NMDA 受体拮抗剂美金刚在挽救突触损伤方面的治疗潜力有限。研究表明,α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)受体在 AD 中也起着重要作用。AMPA 受体的异常转录、表达和定位导致突触功能障碍和损伤,导致 AD 患者的早期认知障碍。了解 AMPA 受体对 AD 发病机制的影响,探索开发 AMPA 受体靶向药物的潜力至关重要。本综述旨在整合最近关于 AD 中 AMPA 受体的研究发现,阐明 AMPA 受体研究的现状,为未来的基础研究和药物开发奠定基础。

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