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.
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 collectively suggest that the miR-16-5p/BCL-2 axis plays an important role for neuronal cell apoptosis in AD.
['Kim|Yeong-Jin|YJ|', 'Kim|So Hee|SH|', 'Park|Yega|Y|', 'Park|Jiyu|J|', 'Lee|Jung Hoon|JH|', 'Kim|Byeong C|BC|', 'Song|Woo Keun|WK|']
D000544:Alzheimer Disease D016229:Amyloid beta-Peptides D000818:Animals D017209:Apoptosis D051379:Mice D035683:MicroRNAs D010446:Peptide Fragments D019253:Proto-Oncogene Proteins c-bcl-2
miR-16-5p Amyloid β Alzheimer's disease Neuronal cell apoptosis BCL-2