Abstract
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.
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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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As shown in Supplementary Fig. S1D, manuscript editor Julian Heng (Remotely Consulting, Australia) provided professional English-language editing of this article (Manuscript Certificate No. 8Ij6Vc8W).
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This work was supported by grants from the Liaoning Province Applied Basic Research Program (NO. 2022JH2/101300013), the General Project of Liaoning Province Education Department (NO. JYTMS20230121), the Natural Science Foundation of Liaoning Province of China (NO. 2021-MS-158), Project of Shenyang Science and Technology Bureau (NO. 202054071), and Project of Shenyang Municipal Health Commission (NO. 2020003).
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L.Z. and T.M. conceived and designed the experiment. L.Z. conducted the experiment. L.Z. and B.Z. analyzed the data. T.M., F.Z., B.Y. and J.C. contributed reagents, materials and analytical tools. L.Z. drafted the manuscript. T.M. and X.Z. helped revise the manuscript. All authors read and approved the final manuscript.
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Zhang, L., Zhu, B., Zhou, X. et al. ZNF787 and HDAC1 Mediate Blood–Brain Barrier Permeability in an In Vitro Model of Alzheimer’s Disease Microenvironment. Neurotox Res 42, 12 (2024). https://doi.org/10.1007/s12640-024-00693-4
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DOI: https://doi.org/10.1007/s12640-024-00693-4