β-Asarone improves learning and memory in Aβ1-42-induced Alzheimer's disease rats by regulating PINK1-Parkin-mediated mitophagy

Metab Brain Dis. 2020 Oct;35(7):1109-1117. doi: 10.1007/s11011-020-00587-2. Epub 2020 Jun 18.

Abstract

Alzheimer's disease (AD) is a chronic neurodegenerative disease that is characterized by the extracellular accumulation of β-amyloid (Aβ). Many studies have shown a close relationship between autophagy and the formation of Aβ. As AD develops and progresses, mitophagy diminishes insoluble Aβ, and mitochondrial dysfunction seems to be a determining factor in the pathogenesis of AD. In our previous study, we showed that β-asarone pharmacological effects in APP/PS1 transgenic mice, reducing Aβ expression. However, the specific mechanism of this effect remains unclear. In this study, AD model rats induced by intracerebroventricular injection of Aβ1-42 were randomly divided into nine groups, and medical intervention was applied to the animals for 30 days. Subsequently, spatial learning and memory were evaluated by the water maze test. Bcl-2 levels in the hippocampus were determined by western blotting (WB). The protein expression of Aβ1-42, Beclin-1, p62, PINK1, and Parkin was assessed by WB and immunohistochemistry (IHC). The data showed that after β-asarone treatment, the learning and memory of the AD rats were clearly improved compared with those of the model group. Moreover, β-asarone decreased Aβ1-42, Bcl-2, and p62 levels but increased Beclin-1 levels compared with those in the model group. In addition, we treated a group of rats with CsA to inhibit mitophagy. β-Asarone increased PINK1 and Parkin expression compared with that in the model group. The results showed that β-asarone can improve the learning and memory of rats with Aβ1-42-induced AD by effectively promoting PINK1-Parkin-mediated mitophagy. Taken together, these results suggest that β-asarone may have the capacity to become a pharmaceutical agent for the treatment of AD in the future.

Keywords: Alzheimer’s disease; Mitophagy; PINK1/Parkin; β-Asarone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allylbenzene Derivatives / pharmacology*
  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Anisoles / pharmacology*
  • Disease Models, Animal
  • Female
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Learning / drug effects*
  • Male
  • Maze Learning / drug effects
  • Memory / drug effects*
  • Mitophagy / drug effects*
  • Neurons / drug effects
  • Peptide Fragments / metabolism
  • Protein Kinases / metabolism
  • Rats
  • Rats, Wistar
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • Allylbenzene Derivatives
  • Amyloid beta-Peptides
  • Anisoles
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • asarone
  • Ubiquitin-Protein Ligases
  • parkin protein
  • Protein Kinases
  • PTEN-induced putative kinase