PDF(Pubmed)
Abstract：
Alzheimer\'s disease (AD) is currently the most common neurodegenerative disease. Glycogen synthase kinase 3β (GSK-3β) is a pivotal factor in AD pathogenesis. Recent research has demonstrated that plant miRNAs exert cross-kingdom regulation on the target genes in animals. Gastrodia elata (G. elata) is a valuable traditional Chinese medicine that has significant pharmacological activity against diseases of the central nervous system (CNS). Our previous studies have indicated that G. elata-specific miRNA plays a cross-kingdom regulatory role for the NF-κB signaling pathway in mice. In this study, further bioinformatics analysis suggested that Gas-miR36-5p targets GSK-3β. Through western blot, RT-qPCR, and assessments of T-AOC, SOD, and MDA levels, Gas-miR36-5p demonstrated its neuroprotective effects in an AD cell model. Furthermore, Gas-miR36-5p was detected in the murine brain tissues. The results of the Morris water maze test and western blot analysis provided positive evidence for reversing the learning deficits and hyperphosphorylation of Tau in AD mice, elucidating significant neuroprotective effects in an AD model following G. elata RNA administration. Our research emphasizes Gas-miR36-5p as a novel G. elata-specific miRNA with neuroprotective properties in Alzheimer\'s disease by targeting GSK-3β. Consequently, our findings provide valuable insights into the cross-kingdom regulatory mechanisms underlying G. elata-specific miRNA, presenting a novel perspective for the treatment of Alzheimer\'s disease.
摘要：
阿尔茨海默病(AD)是目前最常见的神经退行性疾病。糖原合成酶激酶3β(GSK-3β)是AD发病的关键因子。最近的研究表明，植物miRNAs对动物中的靶基因具有跨王国调控作用。天麻(G.elata）是一种有价值的中药，对中枢神经系统（CNS）疾病具有显着的药理活性。我们先前的研究表明，G.elata特异性miRNA在小鼠中对NF-κB信号通路起着跨王国的调节作用。在这项研究中,进一步的生物信息学分析表明，Gas-miR36-5p靶向GSK-3β。通过westernblot,RT-qPCR,以及对T-AOC的评估，SOD,和MDA水平，Gas-miR36-5p在AD细胞模型中证明了其神经保护作用。此外，在鼠脑组织中检测到gas-miR36-5p。Morris水迷宫试验和westernblot分析的结果为逆转AD小鼠学习缺陷和Tau蛋白过度磷酸化提供了阳性证据,阐明G.elataRNA给药后AD模型中的显着神经保护作用。我们的研究强调Gas-miR36-5p是一种新型的G.elata特异性miRNA，通过靶向GSK-3β在阿尔茨海默病中具有神经保护特性。因此,我们的发现提供了有关G.elata特异性miRNA的跨王国调控机制的有价值的见解，为阿尔茨海默病的治疗提供了新的视角。
