Resveratrol attenuates oxidative damage through activating mitophagy in an in vitro model of Alzheimer's disease

Toxicol Lett. 2018 Jan 5:282:100-108. doi: 10.1016/j.toxlet.2017.10.021. Epub 2017 Oct 31.


Alzheimer's disease (AD) is a chronic neurodegenerative disease, which is characterized by the extracellular deposition of β-amyloid (Aβ). Previous studies reported that resveratrol, a natural herbal compound isolated from grapes, could alleviate the development and progression of AD. However, the underlying mechanism is still unclear. In the study, amyloid beta-peptide1-42 (Aβ1-42) -treated the differentiated rat pheochromocytoma cell line (PC12) was chosen as an AD cellular model. Our data showed that resveratrol attenuated Aβ1-42-induced cell death and significantly enhanced mitophagy including an increase in acidic vesicular organelle number, LC3-II/LC3-I ratio, Parkin and Beclin-1 expression, and LC3 and TOMM20 co-localization in Aβ1-42-treated PC12 cells. However, 3-MA remarkably inhibited resveratrol-induced mitophagy. Resveratrol reduced apoptosis, decreased oxidative status and alleviated mitochondrial damage in Aβ1-42-treated PC12 cells. However, all of the protective effects were significantly blocked by 3-MA, suggesting that mitophagy was considerably involved in the neuroprotective effects of resveratrol via decreasing oxidative status. Our study suggests that mitophagy pathway may become a new targeted therapy to attenuate neuronal damage induced by AD.

Keywords: 3-MA; Apoptosis; Autophagy; Aβ1-42; Oxidative stress.

MeSH terms

  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / pharmacology
  • Animals
  • Antioxidants / pharmacology*
  • Cell Culture Techniques
  • Cell Survival / drug effects
  • Membrane Potential, Mitochondrial / drug effects
  • Mitophagy / drug effects*
  • Oxidative Stress / drug effects*
  • PC12 Cells
  • Peptide Fragments / pharmacology
  • Rats
  • Resveratrol
  • Stilbenes / pharmacology*


  • Amyloid beta-Peptides
  • Antioxidants
  • Peptide Fragments
  • Stilbenes
  • amyloid beta-protein (1-42)
  • Resveratrol