miR-16-5p is upregulated by amyloid β deposition in Alzheimer's disease models and induces neuronal cell apoptosis through direct targeting and suppression of BCL-2.

miR-16-5p is upregulated by amyloid β deposition in Alzheimer's disease models and induces neuronal cell apoptosis through direct targeting and suppression of BCL-2. Exp Gerontol. 2020 Apr 19;:110954 Authors: Kim YJ, Kim SH, Park Y, Park J, Lee JH, Kim BC, Song WK Abstract Alzheimer's disease (AD) is the most common form of dementia with irreversible neurodegeneration. Accumulation of amyloid beta (Aβ) in the brain is considered to be a major cause of neuronal cell death in AD, but the neurotoxic mechanism of Aβ is not yet fully understood. Here, we focused on the role of microRNAs (miRNAs) in Aβ-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 Aβ plaque-deposition sites in 5xFAD mouse brains. Aβ 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 co...
Source: Experimental Gerontology - Category: Geriatrics Authors: Tags: Exp Gerontol Source Type: research