Department of Neurology, The First Affiliated Hospital of University of South China, Hengyang, Hunan, China.
Department of Anesthesiology, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan, China.
J Drug Target. 2021 Jun;29(5):531-540. doi: 10.1080/1061186X.2020.1864739. Epub 2021 Jan 11.
It is believed that microRNAs (miRNAs) participate in the pathogenesis of Alzheimer's disease (AD), but the specified function of miR-10b-5p in the disease has not been thoroughly understood. Thereafter, this research aimed to assess the function of miR-10b-5p in AD.
Rat AD models were established by injected with amyloid-β (Aβ), which were mainly treated with lentivirus-miR-10b-5p inhibitor, or lentivirus-overexpressed homeobox D10 (HOXD10). MiR-10b-5p, HOXD10, RhoA, ROCK1 and ROCK2 expression in rat hippocampal tissues were determined. Afterwards, the behaviour of rats was tested, and neuronal apoptosis, pathological injury, and inflammatory factors and oxidative stress-related factors were all assessed. Finally, the target relation between miR-10b-5p and HOXD10 was detected.
MiR-10b-5p was upregulated while HOXD10 was downregulated, and the Rho/ROCK signalling pathway was activated in hippocampal tissues of rats with AD. Inhibition of miR-10b-5p could attenuate the neuronal apoptosis, pathological injury, inflammation reaction, and oxidative stress by elevating HOXD10 and inhibiting the Rho/ROCK signalling pathway in AD rats. Moreover, HOXD10 was targeted by miR-10b-5p.
Inhibited miR-10b-5p decelerated the development of AD by promoting HOXD10 and inactivating the Rho/ROCK signalling pathway, and our findings may contribute to the exploration of AD treatment.
据信 microRNAs(miRNAs)参与阿尔茨海默病(AD)的发病机制,但 miR-10b-5p 在该疾病中的特定功能尚未被充分理解。因此,本研究旨在评估 miR-10b-5p 在 AD 中的功能。
通过注射淀粉样蛋白-β(Aβ)建立大鼠 AD 模型,主要用慢病毒-miR-10b-5p 抑制剂或慢病毒过表达同源盒 D10(HOXD10)进行处理。测定大鼠海马组织中 miR-10b-5p、HOXD10、RhoA、ROCK1 和 ROCK2 的表达。随后,对大鼠的行为进行测试,并评估神经元凋亡、病理损伤以及炎症因子和氧化应激相关因子。最后,检测 miR-10b-5p 和 HOXD10 之间的靶关系。
AD 大鼠海马组织中 miR-10b-5p 上调,HOXD10 下调,Rho/ROCK 信号通路被激活。抑制 miR-10b-5p 可通过上调 HOXD10 和抑制 AD 大鼠中的 Rho/ROCK 信号通路来减轻神经元凋亡、病理损伤、炎症反应和氧化应激。此外,HOXD10 是 miR-10b-5p 的靶标。
抑制 miR-10b-5p 通过促进 HOXD10 和失活 Rho/ROCK 信号通路来减缓 AD 的发展,我们的研究结果可能有助于 AD 治疗的探索。