Anthocyanin-Loaded PEG-Gold Nanoparticles Enhanced the Neuroprotection of Anthocyanins in an Aβ1-42 Mouse Model of Alzheimer's Disease

Mol Neurobiol. 2017 Oct;54(8):6490-6506. doi: 10.1007/s12035-016-0136-4. Epub 2016 Oct 11.

Abstract

Nanomedicine is an emerging research area. In this study, we investigated the neuroprotective efficacy of anthocyanin-loaded polyethylene glycol-gold nanoparticles (PEG-AuNPs) for enhancing the neuroprotective efficacy of anthocyanins in an amyloid beta (Aβ)1-42 mouse model of Alzheimer's disease. We observed that both anthocyanin-loaded PEG-AuNPs and anthocyanins treatment (12 μg/g/day for 14 days) ameliorated memory impairments in the Aβ1-42-injected mice. However, the anthocyanin-loaded PEG-AuNPs were more effective than free anthocyanins. Anthocyanin-loaded PEG-AuNPs protected pre- and post-synaptic proteins from Aβ1-42-induced synaptic dysfunction. Interestingly, the anthocyanin-loaded PEG-AuNPs also regulated the p-PI3K/p-Akt/p-GSK3β pathway and, as a result, prevented the hyperphosphorylation of tau protein at serines 413 and 404 in the Aβ1-42-injected mice. Western blot results of cytochrome c, Bax/Bcl2, caspases and poly (ADP-ribose) polymerase-1 expression levels, and immunohistochemical Nissl and Fluoro-Jade B staining also indicated that the anthocyanin-loaded PEG-AuNPs inhibited apoptosis and neurodegeneration in the Aβ1-42-injected mice. Our results suggest that the conjugation of dietary polyphenolic compounds with gold nanoparticles, such as anthocyanin-loaded PEG-AuNPs, is a novel approach that may represent an important and promising nanomedicine strategy to prevent age-associated neurodegenerative diseases.

Keywords: Alzheimer’s disease; Anthocyanin-PEG-gold nanoparticles; Nanomedicine; Neurodegeneration; Synaptic dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Anthocyanins / administration & dosage
  • Anthocyanins / therapeutic use*
  • Brain / drug effects*
  • Brain / metabolism
  • Disease Models, Animal
  • Gold
  • Male
  • Metal Nanoparticles / administration & dosage*
  • Mice
  • Neuroprotection / drug effects
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / therapeutic use*
  • Peptide Fragments / metabolism*
  • Phosphorylation
  • tau Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • Anthocyanins
  • Neuroprotective Agents
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • tau Proteins
  • Gold