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神经退行性疾病:酸敏感离子通道的潜在治疗作用是什么?

Neurodegenerative Disease: What Potential Therapeutic Role of Acid-Sensing Ion Channels?

作者信息

Mango Dalila, Nisticò Robert

机构信息

Laboratory of Pharmacology of Synaptic Plasticity, European Brain Research Institute, Rome, Italy.

School of Pharmacy, University of Rome "Tor Vergata", Rome, Italy.

出版信息

Front Cell Neurosci. 2021 Oct 8;15:730641. doi: 10.3389/fncel.2021.730641. eCollection 2021.

Abstract

Acidic pH shift occurs in many physiological neuronal activities such as synaptic transmission and synaptic plasticity but also represents a characteristic feature of many pathological conditions including inflammation and ischemia. Neuroinflammation is a complex process that occurs in various neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and Huntington's disease. Acid-sensing ion channels (ASICs) represent a widely expressed pH sensor in the brain that play a key role in neuroinflammation. On this basis, acid-sensing ion channel blockers are able to exert neuroprotective effects in different neurodegenerative diseases. In this review, we discuss the multifaceted roles of ASICs in brain physiology and pathology and highlight ASIC1a as a potential pharmacological target in neurodegenerative diseases.

摘要

酸性pH值变化发生在许多生理神经元活动中,如突触传递和突触可塑性,但它也是许多病理状况的一个特征,包括炎症和缺血。神经炎症是一个复杂的过程,发生在各种神经退行性疾病中,如阿尔茨海默病、帕金森病、多发性硬化症和亨廷顿舞蹈症。酸敏感离子通道(ASICs)是大脑中广泛表达的pH传感器,在神经炎症中起关键作用。在此基础上,酸敏感离子通道阻滞剂能够在不同的神经退行性疾病中发挥神经保护作用。在这篇综述中,我们讨论了ASICs在脑生理和病理中的多方面作用,并强调ASIC1a作为神经退行性疾病潜在的药理学靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/966a/8531221/f324cb27a2d8/fncel-15-730641-g001.jpg

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