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 Jul 15;136:110954. doi: 10.1016/j.exger.2020.110954. Epub 2020 Apr 19.

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 collectively suggest that the miR-16-5p/BCL-2 axis plays an important role for neuronal cell apoptosis in AD.

Keywords: Alzheimer's disease; Amyloid β; BCL-2; Neuronal cell apoptosis; miR-16-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / genetics
  • Amyloid beta-Peptides
  • Animals
  • Apoptosis
  • Mice
  • MicroRNAs* / genetics
  • Peptide Fragments
  • Proto-Oncogene Proteins c-bcl-2 / genetics

Substances

  • Amyloid beta-Peptides
  • MicroRNAs
  • Peptide Fragments
  • Proto-Oncogene Proteins c-bcl-2