Maazouzi Mohamed, Rasheed Madiha, Mbarek Lamia, Wang Xuezhe, Liang Junhan, Ma Hong, Chen Zixuan, Deng Yulin
Beijing Key Laboratory for Separation and Analysis in Biomedicine and Pharmaceuticals, School of Medical Technology, Beijing Institute of Technology, Beijing, People's Republic of China.
Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China.
J Neurochem. 2025 Mar;169(3):e70031. doi: 10.1111/jnc.70031.
Neurodegenerative diseases (NDs) are characterized by progressive neuronal loss and dysfunction, leading to significant cognitive and motor impairments. The disruption of the blood-brain barrier (BBB) integrity, a key regulator of central nervous system homeostasis, emerges as a critical factor in the pathogenesis of these disorders. Accumulating evidence implicates non-coding RNAs, particularly microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), in BBB regulation. However, the intricate network governing BBB dysfunction and consequent neurodegeneration remains obscure. This systematic review maps the convergent microRNA networks in Alzheimer's, Parkinson's, and multiple sclerosis, unveiling their putative roles in BBB modulation. We analyzed data from 11 peer-reviewed clinical studies, identifying key miRNAs such as hsa-miR-155, hsa-miR-22, hsa-miR-146a, hsa-miR-100-3p, and hsa-miR-182-5p as critical regulators of BBB permeability and inflammatory responses. Enrichment analysis revealed that these miRNAs modulate pathways related to inflammation, oxidative stress, and neuronal survival. Our review also uncovered extensive interactions between these miRNAs and transcription factors like JUN, RELA, STAT3, and TP53, as well as lncRNAs such as MALAT1, NEAT1, NORAD, and SNHG16. These interactions highlight complex regulatory networks involving miRNA sponging and chromatin remodeling, which may play crucial roles in maintaining BBB integrity. These analyses underscore the importance of miRNA-mediated regulatory networks in BBB function and offer insights into potential therapeutic targets for NDs.
神经退行性疾病（NDs）的特征是神经元进行性丧失和功能障碍，导致严重的认知和运动障碍。血脑屏障（BBB）完整性的破坏是中枢神经系统稳态的关键调节因子，在这些疾病的发病机制中成为一个关键因素。越来越多的证据表明非编码RNA，特别是微小RNA（miRNA）和长链非编码RNA（lncRNA）参与血脑屏障的调节。然而，控制血脑屏障功能障碍及随之而来的神经退行性变的复杂网络仍不清楚。本系统综述绘制了阿尔茨海默病、帕金森病和多发性硬化症中趋同的微小RNA网络，揭示了它们在血脑屏障调节中的假定作用。我们分析了11项经同行评审的临床研究数据，确定了关键的miRNA，如hsa-miR-155、hsa-miR-22、hsa-miR-146a、hsa-miR-100-3p和hsa-miR-182-5p，它们是血脑屏障通透性和炎症反应的关键调节因子。富集分析表明，这些miRNA调节与炎症、氧化应激和神经元存活相关的途径。我们的综述还发现这些miRNA与JUN、RELA、STAT3和TP53等转录因子以及MALAT1、NEAT1、NORAD和SNHG16等lncRNA之间存在广泛的相互作用。这些相互作用突出了涉及miRNA海绵化和染色质重塑的复杂调控网络，这可能在维持血脑屏障完整性方面发挥关键作用。这些分析强调了miRNA介导的调控网络在血脑屏障功能中的重要性，并为神经退行性疾病的潜在治疗靶点提供了见解。
