Amyloid-β peptide increases cell surface localization of α7 ACh receptor to protect neurons from amyloid β-induced damage

Biochem Biophys Res Commun. 2015 Dec;468(1-2):157-60. doi: 10.1016/j.bbrc.2015.10.141. Epub 2015 Nov 4.

Abstract

Amyloid-β peptide 1-42 (Aβ1-42) reduced PC-12 cell viability in a concentration (1-10 μM)- and treatment time (48-72 h)-dependent manner. Nicotine prevented Aβ1-42-induced PC-12 cell death, but conversely, the α7 ACh receptor antagonist α-bungarotoxin enhanced Aβ1-42-induced cell toxicity. Extracellularly applied Aβ1-42 significantly increased cell surface localization of α7 ACh receptor in PC-12 cells as compared with that for non-treated control cells. Cell surface localization of α7 ACh receptor in the brain of 5xFAD mouse, an animal model of Alzheimer's disease (AD), apparently increased in an age (1-12 months)-dependent manner in association with increased accumulation of Aβ1-42 in the plasma membrane component. Taken together, these results indicate that Aβ1-42 promotes translocation of α7 ACh receptor towards the cell surface and that α7 ACh receptor rescues neuronal cells from Aβ1-42-induced damage.

Keywords: Amyloid-β; Neuronal death; Protection; Translocation; α7 ACh receptor.

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Peptides / pharmacology*
  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Cell Survival / drug effects
  • Mice
  • Neurons / cytology*
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents / metabolism*
  • Neuroprotective Agents / pharmacology*
  • Nicotine / pharmacology
  • PC12 Cells
  • Peptide Fragments / metabolism*
  • Peptide Fragments / pharmacology*
  • Protein Transport / drug effects
  • Rats
  • alpha7 Nicotinic Acetylcholine Receptor / agonists
  • alpha7 Nicotinic Acetylcholine Receptor / analysis
  • alpha7 Nicotinic Acetylcholine Receptor / metabolism*

Substances

  • Amyloid beta-Peptides
  • Neuroprotective Agents
  • Peptide Fragments
  • alpha7 Nicotinic Acetylcholine Receptor
  • amyloid beta-protein (1-42)
  • Nicotine