| First Author | Liu Y | Year | 2019 |
| Journal | Eur J Pharmacol | Volume | 843 |
| Pages | 134-144 | PubMed ID | 30412727 |
| Mgi Jnum | J:268006 | Mgi Id | MGI:6270781 |
| Doi | 10.1016/j.ejphar.2018.11.004 | Citation | Liu Y, et al. (2019) MicroRNA-128 knockout inhibits the development of Alzheimer's disease by targeting PPARgamma in mouse models. Eur J Pharmacol 843:134-144 |
| abstractText | Alzheimer's disease (AD) is a great threat for the health and life of elderly people. MicroRNA-128 (miR-128) has been reported to be abnormally expressed in the brain of AD patients and associated with the pathogenesis of AD. Our study aimed to have a deep insight into the roles and molecular basis of miR-128 in the development and progression of AD. The cognitive ability and exploratory behaviors were assessed by morris water maze and open-field tests, respectively. The concentrations of amyloid-beta (Abeta) 40, Abeta 42, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-10 and activity of beta-secretase and alpha-secretase were determined by corresponding ELISA commercial kits. RT-qPCR assay was performed to detect miR-128 level and the mRNA expression of peroxisome proliferator-activated receptor gamma (PPARgamma), ionized calcium-binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP). Western blot assay was conducted to determine protein expression of PPARgamma, amyloid precursor protein (APP), beta-APP cleaving enzyme (BACE1), sAPPalpha and sAPPbeta. The effect of miR-128 and PPARgamma on amyloid plaque formation was assessed by immunohistochemistry assay. PPARgamma mean optical density was determined by immunofluorescence assay. The interaction between miR-128 and PPARgamma were validated by bioinformatics analysis and luciferase reporter assay. We found AD mice showed AD-like performance and an increased cerebral cortex Abeta production. MiR-128 expression was upregulated and PPARgamma expression was downregulated in cerebral cortex of AD mice. Moreover, PPARgamma was a target of miR-128. Additionally, miR-128 knockout or PPARgamma upregulation inhibited AD-like performances, amyloid plaque formation, Abeta generation, APP amyloidogenic processing and inflammatory responses in AD mice, while these effects of miR-128 knockout were abrogated by PPARgamma inhibitor. The results indicated MiR-128 knockout weakened AD-like performances, and reduced Abeta production and inflammatory responses by targeting PPARgamma in AD mice. |
