阿尔茨海默病脑内γ-氨基丁酸受体的变化

Research Progress of GABA Receptors in Alzheimer’s Disease

阿尔茨海默病(Alzheimer disease,AD)是一种进行性发展的神经系统退行性疾病,主要的临床病理特征为β-淀粉样蛋白(amyloidβ-protein,Aβ)斑块,tau过度磷酸化在细胞内形成神经元纤维缠结。目前,越来越多的证据表明,γ-氨基丁酸(gamma aminobutyric acid,GABA)受体的变化与AD有着紧密的关系,有研究表明,GABA受体中各亚基在AD患者中表达水平有所变化。因此推测,GABA各亚基的变化可能与AD发病机制有关,但目前在临床,仍无较好地通过靶向治疗GABA受体来改善AD的方法。为了进一步了解GABA受体的变化与AD的关系,本文综述了脑内GABA受体在AD患者及动物模型中的变化,发现AD患者的GABA(A)受体亚基中出现了差异性表达。总结AlzheimerDataBase数据库AD中GABA受体各个亚基的改变,基于数据,我们发现少数几个GABA亚基发生了显著性变化。而证据显示,GABA受体的变化改变了脑内的神经活动,另有研究发现,通过GABA受体激动剂与拮抗剂治疗小鼠可以改善小鼠的认知能力。通过总结GABA受体在AD中的差异表达,希望为治疗AD提供更为准确的靶点。

Alzheimer’s disease(AD)is a progressive neurodegenerative disease with the early symptom of Aβplaque,tau hyperphosphorylation neuronal tangle formation in cells.At present,accumulated evidence shows that the changes of GABA receptors are closely related to AD.Some studies have shown that the expression level of each subunit of the GABA receptor changes in AD patients.Therefore,it is speculated that the changes of GABA subunits may be related to the pathogenesis of AD,but there is no better methods to improve AD by targeting GABA receptors.In order to further understand the relationship between the changes of GABA receptors and AD,this paper first reviewed the changes of GABA receptors in AD patients and animal models’brains and found that there was differential expression in GABA(A)receptor subunits in AD patients.Then we summarized the changes of GABA receptor subunits in Alzheimer database.Based on the data,we found that a few GABA subunits had significant changes.The evidence shows that the change of GABA receptors alters the neural activity in the brain.Other studies have found that the treatment of mice with GABA receptor agonists and antagonists can improve the cognitive ability of mice.We hope that understanding the differential expression of GABA receptors in AD will provide a more accurate target for the treatment of AD.