Ma Xiaohui, Liu Linlin, Meng Jing
Department of Geriatrics, Xi'an No. 1 Hospital, Xi'an 710002, China.
Open Ward, Qingdao Mental Health Center, Qingdao 266034, China.
Neurosci Lett. 2017 Nov 20;661:57-62. doi: 10.1016/j.neulet.2017.09.043. Epub 2017 Sep 22.
Alzheimer's disease (AD) is considered as one of the most common neural degenerative diseases in human. Although the continuous investigations about AD have been made in recent decades, the pathogenesis of this disease is still not definitely confirmed. MicroRNA-125b (miR-125b) is extensive expressed in many types of human tissues and played pivotal regulatory roles in diverse biological process. In the present study, we aimed to explore the roles of miR-125b in regulating neurons cell apoptosis under AD condition. The possible molecular mechanisms were also investigated. We found that miR-125b was up-regulated in patients with AD. Transfection with miR-125b significantly enhanced the apoptosis of neurons cells and phosphorylation of Tau by activation of cyclin-dependent kinase 5 (CDK5) and p35/25. Forkhead box Q1 (FOXQ1) was the direct target gene of miR-125b, which involved in the effects of miR-125b on neurons cell apoptosis and phosphorylation of Tau. Our research interpreted the mechanism of up-regulation of miR-125b in pathological Tau phosphorylation and AD occurrence. miR-125b may be a novel regulator of AD progress and could be as a therapeutic target for AD therapy.
阿尔茨海默病(AD)被认为是人类最常见的神经退行性疾病之一。尽管近几十年来对AD进行了持续研究,但该疾病的发病机制仍未得到明确证实。微小RNA-125b(miR-125b)在多种人类组织中广泛表达,并在多种生物学过程中发挥关键调节作用。在本研究中,我们旨在探讨miR-125b在AD条件下调节神经元细胞凋亡中的作用。还研究了可能的分子机制。我们发现AD患者中miR-125b上调。用miR-125b转染可通过激活细胞周期蛋白依赖性激酶5(CDK5)和p35/25显著增强神经元细胞凋亡和Tau蛋白磷酸化。叉头框Q1(FOXQ1)是miR-125b的直接靶基因,其参与了miR-125b对神经元细胞凋亡和Tau蛋白磷酸化的影响。我们的研究解释了miR-125b上调在病理性Tau蛋白磷酸化和AD发生中的机制。miR-125b可能是AD进展的新型调节因子,可作为AD治疗的靶点。