| First Author | Kim YJ | Year | 2020 |
| Journal | Exp Gerontol | Volume | 136 |
| Pages | 110954 | PubMed ID | 32320719 |
| Mgi Jnum | J:311231 | Mgi Id | MGI:6717993 |
| Doi | 10.1016/j.exger.2020.110954 | Citation | Kim YJ, et al. (2020) miR-16-5p is upregulated by amyloid beta deposition in Alzheimer's disease models and induces neuronal cell apoptosis through direct targeting and suppression of BCL-2. Exp Gerontol 136:110954 |
| abstractText | Alzheimer's disease (AD) is the most common form of dementia with irreversible neurodegeneration. Accumulation of amyloid beta (Abeta) in the brain is considered to be a major cause of neuronal cell death in AD, but the neurotoxic mechanism of Abeta is not yet fully understood. Here, we focused on the role of microRNAs (miRNAs) in Abeta-induced neuronal cell death. In microarray and RT-qPCR analysis of plasma miRNAs obtained from 5 familiar AD mutations (5xFAD) and wild-type (WT) mice of various ages, miR-16-5p showed a significant age-related change that was accompanied by neuronal cell death in the brain tissue of 5xFAD mice. In addition, increased miR-16-5p was prominent near Abeta plaque-deposition sites in 5xFAD mouse brains. Abeta treatment induced miR-16-5p upregulation and apoptosis in primary cultured mouse cortical neurons and the SH-SY5Y human neuroblastoma cell line. In silico analysis and reporter gene assays indicated that miR-16-5p directly targets the mRNA encoding the anti-apoptotic factor, B cell lymphoma-2 (BCL-2), in the neuronal cell line. Overexpression of miR-16-5p in SH-SY5Y cells downregulated BCL-2 expression and induced apoptosis. These results collectively suggest that the miR-16-5p/BCL-2 axis plays an important role for neuronal cell apoptosis in AD. |
