Abstract：
Blood-brain barrier (BBB) changes are acknowledged as early indicators of Alzheimer\'s disease (AD). The permeability and integrity of the BBB rely significantly on the essential role played by the tight junction proteins (TJPs) connecting endothelial cells. This study found the reduced RNA binding motif protein 3 (RBM3) expression in brain microvascular endothelial cells (BMECs) incubated with Aβ1-42. This downregulation of RBM3 caused a decrease in the levels of ZO-1 and occludin and increased the permeability of BBB cell model in AD microenvironment. Myocyte enhancer factor 2C (MEF2C) expression was also inhibited in BMECs incubated with Aβ1-42. A decrease in MEF2C expression led to increased permeability of BBB cell model in AD microenvironment and reductions in the levels of ZO-1 and occludin. Further analysis of the underlying mechanism revealed that RBM3 binds to and stabilizes MEF2C mRNA. MEF2C binds to the promoters of ZO-1 and occludin, enhancing their transcriptional activities and modulating BBB permeability. RBM3 increases the stability of MEF2C mRNA and subsequently modulates BBB permeability through the paracellular pathway of TJPs. This may provide new insights for AD research.
摘要：
血脑屏障(BBB)变化被认为是阿尔茨海默病(AD)的早期指标。血脑屏障（BBB）的通透性和完整性在很大程度上取决于连接内皮细胞的紧密连接蛋白（TJPs）所发挥的重要作用。这项研究发现与Aβ1-42孵育的脑微血管内皮细胞（BMEC）中RNA结合基序蛋白3（RBM3）的表达降低。RBM3的下调导致ZO-1和闭塞蛋白水平降低，并增加了AD微环境中BBB细胞模型的通透性。在与Aβ1-42孵育的BMECs中，肌细胞增强因子2C（MEF2C）的表达也受到抑制。MEF2C表达的减少导致AD微环境中BBB细胞模型的通透性增加，ZO-1和occludin水平降低。对潜在机制的进一步分析显示RBM3结合并稳定MEF2CmRNA。MEF2C与ZO-1和occludin的启动子结合，增强其转录活性并调节BBB通透性。RBM3增加MEF2CmRNA的稳定性，随后通过TJPs的细胞旁途径调节BBB通透性。这可能为AD研究提供新的见解。
