Regulation of proapoptotic proteins Bak1 and p53 by miR-125b in an experimental model of Alzheimer's disease: Protective role of 17β-estradiol

Neurosci Lett. 2016 Aug 26:629:234-240. doi: 10.1016/j.neulet.2016.05.049. Epub 2016 May 25.

Abstract

Alzheimer's disease has become one of the most impacting disorders since world population is rapidly aging. MicroRNA-125b plays a crucial role in many cellular processes and pathologies, but, to date, its role in Alzheimer's disease is controversial. In this study, we demonstrated, for the first time, that the down regulation of miR-125b is a key event for the neurotoxic effect of Aβ treatment in cortical neurons. Moreover, we found that 17β-estradiol treatment protects neurons from the Aβ-peptide induced neurotoxicity by increasing miR-125b expression that, in turn, decreased the expression, both at gene and protein levels, of the pro-apoptopic proteins Bak1 and p53. Overall, our data reveal miR-125b as a novel neuro-protector miRNA in Alzheimer's disease.

Keywords: 17β-Estradiol; Alzheimer’ disease; mir-125b.

MeSH terms

  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / toxicity*
  • Animals
  • Apoptosis* / drug effects
  • Cells, Cultured
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / physiopathology
  • Disease Models, Animal
  • Estradiol / administration & dosage*
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / metabolism*
  • Neurons / metabolism
  • Neurons / physiology
  • Peptide Fragments / toxicity*
  • Tumor Suppressor Protein p53 / metabolism*
  • bcl-2 Homologous Antagonist-Killer Protein / metabolism*

Substances

  • Amyloid beta-Peptides
  • Bak1 protein, mouse
  • MicroRNAs
  • Mirn125 microRNA, mouse
  • Peptide Fragments
  • Tumor Suppressor Protein p53
  • amyloid beta-protein (25-35)
  • bcl-2 Homologous Antagonist-Killer Protein
  • Estradiol