Amyloid β-induced miR-16-5p promotes neuronal cell death in 5XFAD mice

Abstract

Alzheimer's disease (AD) is the most common disease of neurodegeneration. Neuronal loss is an important factor of AD pathogenesis, but its underlying molecular mechanism is still unclear. Therefore, we focused on neuronal loss in this study. Recent studies have aimed to elucidate altered miRNA expression in AD. Among the miRNAs studied, miR-16-5p has been implicated in apoptosis by targeting Bcl-2. Human cell lines and a mouse model (5XFAD) were used in this study because human samples were difficult to obtain. First, we isolated brains from 5XFAD mice to identify AD pathology and miR-16-5p expression levels. Amyloid β (Aβ) plaques and neuronal loss were confirmed, and expression levels of miR-16-5p increased with age. To determine why miR-16-5p expression increased with age in 5XFAD mice, differentiated SH-SY5Y cells were used for the following studies. We found that miR-16-5p expression was increased in SH-SY5Y cells after Aβ treatment. As a result, we hypothesized that miR-16-5p was increased by Aβ in old 5XFAD brains, causing neuronal loss. In addition, when the cells were transfected with miR-16-5p mimic, cell death increased, protein levels of Bcl-2 decreased, and the amount of cleaved caspase 3 increased. Taken together, these results propose that miR-16-5p may be induced by Aβ and may promote neuronal cell death by targeting Bcl-2.