Formononetin attenuates Aβ25-35-induced cytotoxicity in HT22 cells via PI3K/Akt signaling and non-amyloidogenic cleavage of APP

Neurosci Lett. 2017 Feb 3:639:36-42. doi: 10.1016/j.neulet.2016.12.064. Epub 2016 Dec 26.

Abstract

Amyloid beta (Aβ) is the main component of the amyloid plaques that accumulate in the brains of Alzheimer patients. Here, we reported the protective role of Formononetin (Form) against Aβ25-35-induced neurotoxicity in HT22 cells. We found that Form significantly increased the viability of HT22 cells but decreased the cell apoptosis when challenging with Aβ25-35. The inhibitory effects of Form were associated with PI3K/Akt signaling pathway as PI3K inhibitor (LY294002) or ERα specific inhibitor (MPP) blocked the effects. Form also accelerated the non-amyloidogenic process of amyloid precursor protein (APP) by enhancing α-secretase activity and sAPPα release. Altogether, our findings may provide a novel therapeutic target to treat AD sufferers.

Keywords: APP; Alzheimer’s disease; ERα; Formononetin; PI3K/Akt; β-amyloid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Peptides / pharmacology*
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Cell Line
  • Isoflavones / pharmacology*
  • Mice
  • Oncogene Protein v-akt / metabolism
  • Peptide Fragments / pharmacology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Signal Transduction / drug effects*

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Isoflavones
  • Peptide Fragments
  • amyloid beta-protein (25-35)
  • formononetin
  • Phosphatidylinositol 3-Kinases
  • Oncogene Protein v-akt