A Preliminary Study of Cu Exposure Effects upon Alzheimer's Amyloid Pathology

Biomolecules. 2020 Mar 6;10(3):408. doi: 10.3390/biom10030408.

Abstract

A large body of evidence indicates that dysregulation of cerebral biometals (Fe, Cu, Zn) and their interactions with amyloid precursor protein (APP) and Aβ amyloid may contribute to the Alzheimer's disease (AD) Aβ amyloid pathology. However, the molecular underpinnings associated with the interactions are still not fully understood. Herein we have further validated the exacerbation of Aβ oligomerization by Cu and H2O2 in vitro. We have also reported that Cu enhanced APP translations via its 5' untranslated region (5'UTR) of mRNA in SH-SY5Y cells, and increased Aβ amyloidosis and expression of associated pro-inflammatory cytokines such as MCP-5 in Alzheimer's APP/PS1 doubly transgenic mice. This preliminary study may further unravel the pathogenic role of Cu in Alzheimer's Aβ amyloid pathogenesis, warranting further investigation.

Keywords: Alzheimer’s disease; Aβ amyloid; amyloid precursor protein; copper; cytokine; neuroinflammation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alzheimer Disease* / genetics
  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / pathology
  • Amyloid beta-Peptides* / chemistry
  • Amyloid beta-Peptides* / genetics
  • Amyloid beta-Peptides* / metabolism
  • Amyloid beta-Protein Precursor* / biosynthesis
  • Amyloid beta-Protein Precursor* / chemistry
  • Amyloid beta-Protein Precursor* / genetics
  • Animals
  • Cell Line, Tumor
  • Copper / toxicity*
  • Female
  • Humans
  • Mice
  • Mice, Transgenic
  • Protein Biosynthesis*
  • Protein Multimerization / drug effects*

Substances

  • APP protein, human
  • APP protein, mouse
  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Copper