α7烟碱型乙酰胆碱受体与阿尔茨海默病的关系  

Relationship between alpha7 nicotinic acetylcholine receptor and Alzheimer’s disease

作　　者：张松江[1] 李龙洋 周春光 Zhang Songjiang;Li Longyang;Zhou Chunguang(Medical College,Henan University of Chinese Medicine,Zhengzhou 450046,Henan Province,China)

机构地区：[1]河南中医药大学医学院,河南省郑州市450046

出　　处：《中国组织工程研究》2025年第18期3915-3924,共10页Chinese Journal of Tissue Engineering Research

基　　金：河南省重点科技攻关项目(152102310100),项目负责人:张松江。

摘　　要：背景:α7烟碱型乙酰胆碱受体在大脑皮质和海马高度表达,并在阿尔茨海默病的病理发展过程中起重要调控作用,是阿尔茨海默病治疗的潜在靶点。目的:总结α7烟碱型乙酰胆碱受体和阿尔茨海默病的密切关系和相互作用机制。方法:检索中国知网、PubMed数据库中相关文献,中文检索词为“α7烟碱型乙酰胆碱受体,阿尔茨海默病,β-淀粉样蛋白,激动剂,正变构调节剂,拮抗剂”;英文检索词为“alpha 7 nicotinic acetylcholine receptor,Alzheimer’s disease,beta amyloid protein,agonist,positive allosteric modulator,antagonist”,文献检索时限为各数据库建库至2024年7月,依据入选标准对检索结果进行录用或排除,最终纳入符合标准的83篇文献进行综述。结果与结论:α7烟碱型乙酰胆碱受体通过与β-淀粉样蛋白的相互作用减轻β-淀粉样蛋白的神经毒性,如促进阿尔茨海默病的突触可塑性和胆碱能突触的快速传递、减轻β-淀粉样蛋白诱导的神经中枢炎症反应、抵抗神经细胞凋亡,从而对阿尔茨海默病患者的脑具有保护作用等。α7烟碱型乙酰胆碱受体作为阿尔茨海默病治疗靶标具有很大的潜能,但是又存在一系列问题有待解决,比如α7烟碱型乙酰胆碱受体的脱敏性、适度活性稳定性及基因多态性等问题。筛选高特异、安全性和以α7烟碱型乙酰胆碱受体为核心的多靶点结合作用的药物,将成为未来阿尔茨海默病治疗研究的一个方向。BACKGROUND:Theα7 nicotinic acetylcholine receptor is highly expressed in the cerebral cortex and hippocampus,and has been shown to play an important regulatory role in the pathological development of Alzheimer’s disease,making it a potential therapeutic target for Alzheimer’s disease.OBJECTIVE:To summarize the close relationship and interaction mechanism betweenα7 nicotinic acetylcholine receptor and Alzheimer’s disease.METHODS:Retrieve relevant literature was searched in CNKI and PubMed databases using the search terms of“alpha7 nicotinic acetylcholine receptor,Alzheimer’s disease,beta amyloid protein,agonist,positive allosteric modulator,antagonist”in Chinese and English,respectively.The search time was from database inception to July 2024.According to the inclusion criteria,the search results were accepted or excluded,and ultimately 83 articles that met the criteria were included for review.RESULTS AND CONCLUSION:Theα7 nicotinic acetylcholine receptor interacts withβ-amyloid protein to reduce the neurotoxicity ofβ-amyloid protein,such as promoting synaptic plasticity and rapid transmission of cholinergic synapses in Alzheimer’s disease,alleviating central nervous system inflammation induced byβ-amyloid protein,resisting neuronal apoptosis,and thus having a protective effect on the brain of patients with Alzheimer’s disease.Theα7 nicotinic acetylcholine receptor has great potential as a therapeutic target for Alzheimer’s disease,but there are still a series of issues that need to be addressed,such as desensitization ofα7 nicotinic acetylcholine receptor,stability of moderate activity,and gene polymorphism.Screening for drugs with high specificity,safety and multi-target binding action centered on theα7 nicotinic acetylcholine receptor will be a future direction for the treatment of Alzheimer’s disease.

关 键 词：7烟碱型乙酰胆碱受体 阿尔茨海默病 Β-淀粉样蛋白 完全激动剂 部分激动剂 沉默激动剂 正变构调节剂 拮抗剂 工程化组织构建 

分 类 号：R459.9[医药卫生—治疗学] R319[医药卫生—临床医学] R741