Beta-asarone protection against beta-amyloid-induced neurotoxicity in PC12 cells via JNK signaling and modulation of Bcl-2 family proteins

Eur J Pharmacol. 2010 Jun 10;635(1-3):96-102. doi: 10.1016/j.ejphar.2010.03.013. Epub 2010 Mar 20.

Abstract

Neurodegenerative brain disorders such as Alzheimer's disease have been well investigated. However, significant methods for the treatment of the promotion and progression of Alzheimer's disease are unavailable to date. Apoptosis is a crucial pathway in neuronal loss in Alzheimer's disease patients. Thus, the suppression of apoptosis may be an effective therapeutic strategy for Alzheimer's disease. In this study, we evaluated the effect of beta-asarone on beta-amyloid (Abeta)-induced toxicity in cultured PC12 cells. Our data show significant induction of apoptosis in PC12 cells incubated with Abeta peptide, and this effect was reduced by beta-asarone. Beta-asarone reduced Abeta-induced JNK activation. In addition, beta-asarone attenuates Abeta-induced down-regulation of Bcl-w and Bcl-xL in a JNK-dependent manner, and subsequent inhibition mitochondrial release of cytochrome c and activation of caspase-3. Together, these findings indicate that Abeta-induced apoptosis of PC12 cells proceeds through mitochondrial pathway. Further, the JNK signaling cascade plays a role in regulating the anti-apoptotic effects of beta-asarone. Thus, our results indicate that beta-asarone might be a potentially therapeutic compound for Alzheimer's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allylbenzene Derivatives
  • Amyloid beta-Peptides / toxicity*
  • Animals
  • Anisoles / pharmacology*
  • Apoptosis / drug effects
  • Cytochromes c / metabolism
  • Gene Expression Regulation / drug effects
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • MAP Kinase Signaling System / drug effects*
  • Neurotoxins / toxicity*
  • PC12 Cells
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Rats
  • bcl-X Protein / genetics
  • bcl-X Protein / metabolism

Substances

  • Allylbenzene Derivatives
  • Amyloid beta-Peptides
  • Anisoles
  • Bcl2l2 protein, rat
  • Neurotoxins
  • Proto-Oncogene Proteins c-bcl-2
  • asarone
  • bcl-X Protein
  • Cytochromes c
  • JNK Mitogen-Activated Protein Kinases