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兴奋性毒性的分子机制及其与神经退行性疾病发病机制的相关性——最新进展

Molecular mechanisms of excitotoxicity and their relevance to the pathogenesis of neurodegenerative diseases-an update.

作者信息

Wu Wei-Long, Gong Xiao-Xi, Qin Zheng-Hong, Wang Yan

机构信息

Department of Pharmacology, College of Pharmaceutical Sciences, Suzhou Key Laboratory of Aging and Nervous Diseases, and Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, Soochow University, Suzhou, 215123, China.

出版信息

Acta Pharmacol Sin. 2025 May 19. doi: 10.1038/s41401-025-01576-w.


DOI:10.1038/s41401-025-01576-w
PMID:40389567
Abstract

Glutamate excitotoxicity is intricately linked to the pathogenesis of neurodegenerative diseases, exerting a profound influence on cognitive functions such as learning and memory in mammals. Glutamate, while crucial for these processes, can lead to neuronal damage and death when present in excessive amounts. Our previous review delved into the cascade of excitotoxic injury events and the underlying mechanisms of excitotoxicity. Building on that foundation, this update summarizes the latest research on the role of excitotoxicity in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, as well as new cutting-edge techniques applied in the study of excitotoxicity. We also explore the mechanisms of action of various excitotoxicity inhibitors and their clinical development status. This comprehensive analysis aims to enhance our understanding of the nexus between excitotoxicity and neurodegenerative diseases, offering valuable insights for therapeutic strategies in these conditions.

摘要

谷氨酸兴奋性毒性与神经退行性疾病的发病机制密切相关,对哺乳动物的学习和记忆等认知功能产生深远影响。谷氨酸虽然对这些过程至关重要,但过量存在时会导致神经元损伤和死亡。我们之前的综述深入探讨了兴奋性毒性损伤事件的级联反应以及兴奋性毒性的潜在机制。在此基础上,本更新总结了关于兴奋性毒性在阿尔茨海默病、帕金森病、亨廷顿病和肌萎缩侧索硬化等神经退行性疾病中的作用的最新研究,以及在兴奋性毒性研究中应用的新的前沿技术。我们还探讨了各种兴奋性毒性抑制剂的作用机制及其临床开发状况。这一全面分析旨在加深我们对兴奋性毒性与神经退行性疾病之间联系的理解,为这些疾病的治疗策略提供有价值的见解。

相似文献

[1]
Molecular mechanisms of excitotoxicity and their relevance to the pathogenesis of neurodegenerative diseases-an update.

Acta Pharmacol Sin. 2025-5-19

[2]
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Aging Dis. 2024-8-8

[3]
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Curr Pharm Des. 2020

[4]
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Front Cell Neurosci. 2020-4-24

[5]
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[6]
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[7]
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[8]
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J Alzheimers Dis. 2004-4

[9]
[Role of glutamate and excitotoxicity in neurologic diseases].

Rev Neurol (Paris). 1996-4

[10]
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[2]
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Sci Adv. 2025-3-7

[3]
KA-mediated excitotoxicity induces neuronal ferroptosis through activation of ferritinophagy.

CNS Neurosci Ther. 2024-9

[4]
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[5]
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[6]
Regulation of FSP1 myristoylation by NADPH: A novel mechanism for ferroptosis inhibition.

Redox Biol. 2024-7

[7]
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[8]
γ-Oryzanol from Rice Bran Antagonizes Glutamate-Induced Excitotoxicity in an In Vitro Model of Differentiated HT-22 Cells.

Nutrients. 2024-4-21

[9]
Excitotoxic glutamate levels cause the secretion of resident endoplasmic reticulum proteins.

J Neurochem. 2024-9

[10]
APOE4/4 is linked to damaging lipid droplets in Alzheimer's disease microglia.

Nature. 2024-4

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