Osthole promotes neuronal differentiation and inhibits apoptosis via Wnt/β-catenin signaling in an Alzheimer's disease model

Toxicol Appl Pharmacol. 2015 Dec 15;289(3):474-81. doi: 10.1016/j.taap.2015.10.013. Epub 2015 Oct 23.

Abstract

Neurogenesis is the process by which neural stem cells (NSCs) proliferate and differentiate into neurons. This is diminished in several neurodegenerative disorders such as Alzheimer's disease (AD), which is characterized by the deposition of amyloid (A)β peptides and neuronal loss. Stimulating NSCs to replace lost neurons is therefore a promising approach for AD treatment. Our previous study demonstrated that osthole modulates NSC proliferation and differentiation, and may reduce Aβ protein expression in nerve cells. Here we investigated the mechanism underlying the effects of osthole on NSCs. We found that osthole enhances NSC proliferation and neuronal differentiation while suppressing apoptosis, effects that were exerted via activation of Wnt/β-catenin signaling. These results provide evidence that osthole can potentially be used as a therapeutic agent in the treatment of AD and other neurodegenerative disorders.

Keywords: Alzheimer's disease; Differentiation; Neural stem cells; Neurons; Osthole; Proliferation; Wnt/β-catenin signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Apoptosis / drug effects*
  • Cell Differentiation / drug effects*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Coumarins / pharmacology*
  • Disease Models, Animal
  • Mice
  • Mice, Inbred C57BL
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / metabolism
  • Neurogenesis / drug effects*
  • Neurons / drug effects
  • Neurons / metabolism
  • Wnt Signaling Pathway / drug effects*
  • beta Catenin / metabolism*

Substances

  • Amyloid beta-Peptides
  • Coumarins
  • beta Catenin
  • osthol