Jujuboside a promotes proliferation and neuronal differentiation of APPswe-overexpressing neural stem cells by activating Wnt/β-catenin signaling pathway

Neurosci Lett. 2022 Feb 16:772:136473. doi: 10.1016/j.neulet.2022.136473. Epub 2022 Jan 22.

Abstract

Mobilization of hippocampal neurogenesis has been considered as a potential strategy for the treatment of neurodegenerative diseases, including Alzheimer's disease (AD). In present study, we evaluated both the neuroprotective effects and the effects on the proliferation and differentiation of APP-overexpressing neural stem cells (APP-NSCs) by Jujuboside A (JuA) in vitro. Our results demonstrated that JuA (50 μM) decreased apoptosis and suppressed oxidative stress damage of APP-NSCs. JuA (50 μM) upregulated the secretion of brain-derived neurotrophic factor and promoted the proliferation and neuronal differentiation of APP-NSCs. Moreover, JuA (50 μM) upregulated Wnt-3a and β-catenin protein expression, and enhanced the expression of downstream genes Ccnd1, Neurod1 and Prox1. However, XAV-939, an inhibitor of the Wnt/β-catenin signaling pathway, inhibited these positive effects of JuA. Taken together, these findings suggest that JuA promote proliferation and neuronal differentiation of APP-NSCs partly by activating the Wnt/β-catenin signaling pathway. We hope that this study will provide a viable strategy for the treatment of AD.

Keywords: Alzheimer’s disease; Differentiation; Jujuboside A; Neural stem cell; Proliferation; Wnt/β-catenin signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Line, Tumor
  • Cell Proliferation*
  • Cells, Cultured
  • Female
  • Heterocyclic Compounds, 3-Ring / pharmacology
  • Hippocampus / cytology
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neural Stem Cells / cytology
  • Neural Stem Cells / drug effects*
  • Neural Stem Cells / metabolism
  • Neural Stem Cells / physiology
  • Neurogenesis*
  • Saponins / pharmacology*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism
  • Wnt Signaling Pathway*
  • beta Catenin / metabolism

Substances

  • APP protein, mouse
  • Amyloid beta-Protein Precursor
  • Basic Helix-Loop-Helix Transcription Factors
  • Heterocyclic Compounds, 3-Ring
  • Homeodomain Proteins
  • Neurod1 protein, mouse
  • Saponins
  • Tumor Suppressor Proteins
  • XAV939
  • beta Catenin
  • prospero-related homeobox 1 protein
  • jujuboside A