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，其特征是与整体脑损伤相关的进行性认知能力下降。最初，由过度磷酸化的 tau 蛋白和细胞外淀粉样蛋白-β (Aβ) 沉积物组成的细胞内成对螺旋丝被认为是 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于直接针对Aβ和tau蛋白，但迄今为止尚未报道有效的治疗方法。因此，目前 AD 患者只能进行姑息治疗。近年来，多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 AD 脑病理学。在该系中，在 AD 患者和 AD 小鼠模型中均发现 P2X7R 的表达水平和功能发生改变。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。在这篇评论中，我们概述了有关 P2X7R 在 AD 中的作用的当前知识。