Francistiová Linda, Bianchi Carolina, Di Lauro Caterina, Sebastián-Serrano Álvaro, de Diego-García Laura, Kobolák Julianna, Dinnyés András, Díaz-Hernández Miguel
BioTalentum Ltd., Gödöllõ, Hungary.
Szent István University, Gödöllõ, Hungary.
Front Mol Neurosci. 2020 Jun 3;13:94. doi: 10.3389/fnmol.2020.00094. eCollection 2020.
Alzheimer's disease (AD) is the most prevalent neurodegenerative disease characterized by a progressive cognitive decline associated with global brain damage. Initially, intracellular paired helical filaments composed by hyperphosphorylated tau and extracellular deposits of amyloid-β (Aβ) were postulated as the causing factors of the synaptic dysfunction, neuroinflammation, oxidative stress, and neuronal death, detected in AD patients. Therefore, the vast majority of clinical trials were focused on targeting Aβ and tau directly, but no effective treatment has been reported so far. Consequently, only palliative treatments are currently available for AD patients. Over recent years, several studies have suggested the involvement of the purinergic receptor P2X7 (P2X7R), a plasma membrane ionotropic ATP-gated receptor, in the AD brain pathology. In this line, altered expression levels and function of P2X7R were found both in AD patients and AD mouse models. Consequently, genetic depletion or pharmacological inhibition of P2X7R ameliorated the hallmarks and symptoms of different AD mouse models. In this review, we provide an overview of the current knowledge about the role of the P2X7R in AD.
阿尔茨海默病（AD）是最常见的神经退行性疾病，其特征是与全脑损伤相关的进行性认知衰退。最初，由过度磷酸化的tau组成的细胞内双螺旋丝和β-淀粉样蛋白（Aβ）的细胞外沉积物被假定为AD患者中检测到的突触功能障碍、神经炎症、氧化应激和神经元死亡的致病因素。因此，绝大多数临床试验都集中在直接靶向Aβ和tau，但迄今为止尚未报告有效的治疗方法。因此，目前AD患者只能接受姑息治疗。近年来，几项研究表明嘌呤能受体P2X7（P2X7R），一种质膜离子型ATP门控受体，参与了AD脑病理学。在这方面，在AD患者和AD小鼠模型中都发现了P2X7R的表达水平和功能改变。因此，P2X7R的基因缺失或药理学抑制改善了不同AD小鼠模型的特征和症状。在这篇综述中，我们概述了目前关于P2X7R在AD中的作用的知识。
