Xiong Jia-Rui, Yan Zi-Yi, Shi Meng-Qiong, Zhou Gang, Zhang Ji-Hong, Xu Jie, Liao Yong, Tang Hai-Ming
Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University & College of Basic Medical Sciences, Yichang, 443002, China.
Renhe Hospital Affiliated to China Three Gorges University, Yichang, 443001, China.
Curr Med Sci. 2025 Jul 9. doi: 10.1007/s11596-025-00080-w.
Neurodegenerative diseases (NDDs) are characterized primarily by progressive impairments in cognition, behavior, and memory. MicroRNAs (miRNAs) are abundantly expressed in the central nervous system and are vital for the normal function and survival of neurons. Mature miRNAs are naturally occurring small noncoding single-stranded RNA molecules that are approximately 21-25 nucleotides in length. They regulate gene expression by pairing with target mRNAs and undergo significant alterations in various physiological and pathological processes. miR-146a, a miRNA dependent on nuclear factor κB (NF-κB), is highly expressed in neurons and functions as an anti-inflammatory miRNA via the Toll-like receptor (TLR) pathway, which is an essential regulatory factor for neuroinflammation expression during the development of NDDs. In this review, we summarize and emphasize the pivotal role of miR-146a in NDDs, highlighting the association between miR-146a polymorphisms and the risk of NDDs. We also discuss how alterations in miR-146a expression levels represent a critical event in the pathogenesis of numerous NDDs. Furthermore, the target genes of miR-146a are involved in regulating the pathophysiological processes of these diseases, particularly in the context of neuroinflammatory responses. In conclusion, miR-146a plays a central role in the progression of NDDs, with its primary function in neuroinflammation. These findings suggest that miR-146a holds promise as both a biomarker and a potential therapeutic target. A deeper understanding of how miR-146a influences neuroinflammatory responses across different types of neurological damage, cell types, and even various stages of certain NDDs will pave the way for its use as a therapeutic target in treating these conditions. Therefore, this article reviews the mechanism of miR-146a in NDDs and discusses the future therapeutic prospects for this type of disease. miR-146a regulates the related genes of the inflammatory signaling pathway and its influence on the development of NDDs. (Created in https://BioRender.com ).
神经退行性疾病（NDDs）的主要特征是认知、行为和记忆逐渐受损。微小RNA（miRNAs）在中枢神经系统中大量表达，对神经元的正常功能和存活至关重要。成熟的miRNAs是天然存在的小非编码单链RNA分子，长度约为21-25个核苷酸。它们通过与靶mRNA配对来调节基因表达，并在各种生理和病理过程中发生显著变化。miR-146a是一种依赖核因子κB（NF-κB）的miRNA，在神经元中高度表达，并通过Toll样受体（TLR）途径作为抗炎miRNA发挥作用，该途径是NDDs发生过程中神经炎症表达的重要调节因子。在本综述中，我们总结并强调了miR-146a在NDDs中的关键作用，突出了miR-146a多态性与NDDs风险之间的关联。我们还讨论了miR-146a表达水平的改变如何代表众多NDDs发病机制中的关键事件。此外，miR-146a的靶基因参与调节这些疾病的病理生理过程，特别是在神经炎症反应的背景下。总之，miR-146a在NDDs的进展中起着核心作用，其主要功能是在神经炎症方面。这些发现表明，miR-146a有望成为生物标志物和潜在的治疗靶点。更深入地了解miR-146a如何在不同类型的神经损伤、细胞类型甚至某些NDDs的不同阶段影响神经炎症反应，将为其作为治疗这些疾病的靶点铺平道路。因此，本文综述了miR-146a在NDDs中的作用机制，并讨论了这类疾病未来的治疗前景。miR-146a调节炎症信号通路的相关基因及其对NDDs发展的影响。（创建于https://BioRender.com ）
