The miR-124 regulates the expression of BACE1/β-secretase correlated with cell death in Alzheimer's disease

Toxicol Lett. 2012 Feb 25;209(1):94-105. doi: 10.1016/j.toxlet.2011.11.032. Epub 2011 Dec 8.

Abstract

The role of miR-124 on the expression of β-site APP cleaving enzyme 1 (BACE1), an important cleavager of amyloid precursor protein that plays a pivotal role in the β-amyloid production, was studied in this paper using cellular models for Alzheimer' disease (AD) of cultured PC12 cell lines and primary cultured hippocampal neurons. The aim of the present study was to uncover novel potential miR-124 targets and shed light on its function in the cellular AD model. MiR-124 expression was steadily altered when its mimic and inhibitor were transfected in vitro. The results showed the expression of BACE1, one of the potential functional downstream targets of miR-124, was well correlated with cell death induced by Aβ neurotoxicity, and its expression level could be up- and down-regulated by suppression or over expression of miR-124 level respectively. These findings suggest that miR-124 may work as a basilic regulating factor to alleviate cell death in the process of AD by targeting BACE1, play an essential role in the control of BACE1 gene expression, and might be considered as a novel therapeutic target in treating AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / pathology*
  • Amyloid Precursor Protein Secretases / biosynthesis
  • Amyloid Precursor Protein Secretases / genetics*
  • Amyloid Precursor Protein Secretases / physiology
  • Animals
  • Apoptosis / drug effects
  • Aspartic Acid Endopeptidases / biosynthesis
  • Aspartic Acid Endopeptidases / genetics*
  • Aspartic Acid Endopeptidases / physiology
  • Blotting, Western
  • Brain / cytology
  • Cell Death / genetics
  • Coloring Agents
  • Fluorescent Antibody Technique
  • Gene Expression Regulation / physiology
  • In Situ Nick-End Labeling
  • MicroRNAs / genetics*
  • Necrosis
  • PC12 Cells
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Tetrazolium Salts
  • Thiazoles
  • Transfection

Substances

  • Coloring Agents
  • MIRN124 microRNA, human
  • MicroRNAs
  • Tetrazolium Salts
  • Thiazoles
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human
  • thiazolyl blue