The permeability of the blood–brain barrier (BBB) is increased in Alzheimer’s disease (AD). This plays a key role in the instigation and maintenance of chronic inflammation during AD. Experiments using AD models showed that the increased permeability of the BBB was mainly caused by the decreased expression of tight junction-related proteins occludin and claudin-5. In this study, we found that ZNF787 and HDAC1 were upregulated in β-amyloid (Aβ)_1–42-incubated endothelial cells, resulting in increased BBB permeability. Conversely, the silencing of ZNF787 and HDAC1 by RNAi led to reduced BBB permeability. The silencing of ZNF787 and HDAC1 enhanced the expression of occludin and claudin-5. Mechanistically, ZNF787 binds to promoter regions for occludin and claudin-5 and functions as a transcriptional regulator. Furthermore, we demonstrate that ZNF787 interacts with HDAC1, and this resulted in the downregulation of the expression of genes encoding tight junction-related proteins to increase in BBB permeability. Taken together, our study identifies critical roles for the interaction between ZNF787 and HDAC1 in regulating BBB permeability and the pathogenesis of AD.

阿尔茨海默病 (AD) 中血脑屏障 (BBB) 的通透性增加。这在 AD 期间慢性炎症的引发和维持中起着关键作用。 AD模型实验表明，BBB通透性增加主要是由于紧密连接相关蛋白occludin和claudin-5表达减少所致。在这项研究中，我们发现 ZNF787 和 HDAC1 在 β-淀粉样蛋白 (Aβ) _1-42孵育的内皮细胞中上调，导致 BBB 通透性增加。相反，RNAi 沉默 ZNF787 和 HDAC1 导致 BBB 通透性降低。 ZNF787和HDAC1的沉默增强了occludin和claudin-5的表达。从机制上讲，ZNF787 与 occludin 和 claudin-5 的启动子区域结合，并充当转录调节因子。此外，我们证明 ZNF787 与 HDAC1 相互作用，导致编码紧密连接相关蛋白的基因表达下调，从而增加 BBB 通透性。综上所述，我们的研究确定了 ZNF787 和 HDAC1 之间的相互作用在调节 BBB 通透性和 AD 发病机制中的关键作用。