MicroRNA-146a represses LRP2 translation and leads to cell apoptosis in Alzheimer's disease

FEBS Lett. 2016 Jul;590(14):2190-200. doi: 10.1002/1873-3468.12229. Epub 2016 Jul 8.


MicroRNA regulation of transcript expression has been reported in patients with Alzheimer's disease (AD). Here, we investigate the role of microRNA-146a (miRNA-146a), a brain-enriched miRNA, which is upregulated in AD patients. Through analysis of predicted targets of miRNA-146a, low-density lipoprotein receptor-related protein-2 (Lrp2), a member of the LDLR family that is known to play a protective role in AD, was identified. Overexpression of miRNA-146a in SH-SY5Y cells significantly decreased Lrp2 expression, resulting in a reduction of Akt activation and induction of proapoptotic caspase-3, thereby increasing cell apoptosis. Thus, specific miRNA-146a regulation may contribute to AD by downregulating the Lrp2/Akt pathway.

Keywords: Alzheimer's disease; Lrp2; apoptosis; miRNA-146a.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Apoptosis*
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Line
  • Humans
  • Low Density Lipoprotein Receptor-Related Protein-2 / biosynthesis*
  • Low Density Lipoprotein Receptor-Related Protein-2 / genetics
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Protein Biosynthesis*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / genetics
  • Up-Regulation*


  • LRP2 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-2
  • MIRN146 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-akt
  • CASP3 protein, human
  • Caspase 3