Angiopoietin-1 accelerates Alzheimer's disease via FOXA2/PEN2/APP pathway in APP/PS1 mice

Life Sci. 2020 Apr 1:246:117430. doi: 10.1016/j.lfs.2020.117430. Epub 2020 Feb 18.

Abstract

Angiopoietin-1 (Ang-1), a regulatory angiogenesis protein and it has been found to be involved in the occurrence and progression of Alzheimer's disease. However, it was still to be addressed the distinctly role and the molecular mechanisms of Ang-1 affects Alzheimer's disease. Our data suggest that Ang-1 aggravated the accumulation of Aβ42 and cognitive decline in APP/PS1 mice. The upregulation of APPβ is essential for Aβ42 production in N2a cells overexpressing the mutational human APP gene (N2a/APP695 cells), while downregulation of PEN2 could reduce APP expression. Silencing of FOXA2 lead to inhibition of APP expression, as well as decrease of Aβ42 contents. In conclusion, Ang-1 has an accelerative effect on Alzheimer's disease by increasing the secretion of Aβ42 via FOXA2/PEN2/APP pathway.

Keywords: Alzheimer's disease; Amyloid precursor protein; Angiopoietin-1; Forkhead box protein A2; Presenilin enhancer protein 2; β-Amyloid peptide.

MeSH terms

  • Alzheimer Disease / etiology*
  • Alzheimer Disease / metabolism
  • Amyloid Precursor Protein Secretases / metabolism*
  • Amyloid Precursor Protein Secretases / physiology
  • Amyloid beta-Protein Precursor / metabolism*
  • Amyloid beta-Protein Precursor / physiology
  • Angiopoietin-1 / physiology*
  • Animals
  • Blotting, Western
  • Brain / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Fluorescent Antibody Technique
  • Hepatocyte Nuclear Factor 3-beta / metabolism*
  • Hepatocyte Nuclear Factor 3-beta / physiology
  • Maze Learning
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction*

Substances

  • Amyloid beta-Protein Precursor
  • Angiopoietin-1
  • Angpt1 protein, mouse
  • Foxa2 protein, mouse
  • Hepatocyte Nuclear Factor 3-beta
  • Amyloid Precursor Protein Secretases