INSERM, CNRS, Institut de la Vision, Sorbonne University, F-75012 Paris, France.
Int J Mol Sci. 2023 Jul 21;24(14):11747. doi: 10.3390/ijms241411747.
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by impaired episodic memory and two pathological lesions: amyloid plaques and neurofibrillary tangles. In AD, damaged neurons and the accumulation of amyloid β (Aβ) peptides cause a significant release of high amounts of extracellular ATP, which acts as a danger signal. The purinergic receptor P2X7 is the main sensor of high concentrations of ATP, and P2X7 has been shown to be upregulated in the brains of AD patients, contributing to the disease's pathological processes. Further, there are many polymorphisms of the gene that impact the risk of developing AD. P2X7 can directly modulate Aβ plaques and Tau protein lesions as well as the inflammatory response by regulating NLRP3 inflammasome and the expression of several chemokines. The significant role of microglial P2X7 in AD has been well established, although other cell types may also be important in P2X7-mediated mechanisms. In this review, we will discuss the different P2X7-dependent pathways involved in the development of AD.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征是情景记忆受损和两种病理损伤：淀粉样斑块和神经原纤维缠结。在 AD 中，受损的神经元和淀粉样 β（Aβ）肽的积累导致大量细胞外 ATP 的显著释放，ATP 作为危险信号起作用。嘌呤能受体 P2X7 是高浓度 ATP 的主要传感器，并且已经表明 P2X7 在 AD 患者的大脑中上调，有助于疾病的病理过程。此外， 基因的许多多态性影响发生 AD 的风险。P2X7 可以通过调节 NLRP3 炎性小体和几种趋化因子的表达，直接调节 Aβ斑块和 Tau 蛋白病变以及炎症反应。小胶质细胞 P2X7 在 AD 中的重要作用已经得到很好的确立，尽管其他细胞类型在 P2X7 介导的机制中也可能很重要。在这篇综述中，我们将讨论参与 AD 发展的不同 P2X7 依赖性途径。
