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Cellular and Molecular Neurobiology

, Volume 37, Issue 2, pp 211–222 | Cite as

Reversal of Beta-Amyloid-Induced Neurotoxicity in PC12 Cells by Curcumin, the Important Role of ROS-Mediated Signaling and ERK Pathway

  • Cun-dong Fan
  • Yuan Li
  • Xiao-ting Fu
  • Qing-jian Wu
  • Ya-jun Hou
  • Ming-feng Yang
  • Jing-yi Sun
  • Xiao-yan FuEmail author
  • Zun-cheng ZhengEmail author
  • Bao-liang SunEmail author
Original Research

Abstract

Progressive accumulation of beta-amyloid (Aβ) will form the senile plaques and cause oxidative damage and neuronal cell death, which was accepted as the major pathological mechanism to the Alzheimer’s disease (AD). Hence, inhibition of Aβ-induced oxidative damage and neuronal cell apoptosis by agents with potential antioxidant properties represents one of the most effective strategies in combating human AD. Curcumin (Cur) a natural extraction from curcuma longa has potential of pharmacological efficacy, including the benefit to antagonize Aβ-induced neurotoxicity. However, the molecular mechanism remains elusive. The present study evaluated the protective effect of Cur against Aβ-induced cytotoxicity and apoptosis in PC12 cells and investigated the underlying mechanism. The results showed that Cur markedly reduced Aβ-induced cytotoxicity by inhibition of mitochondria-mediated apoptosis through regulation of Bcl-2 family. The PARP cleavage, caspases activation, and ROS-mediated DNA damage induced by Aβ were all significantly blocked by Cur. Moreover, regulation of p38 MAPK and AKT pathways both contributed to this protective potency. Our findings suggested that Cur could effectively suppress Aβ-induced cytotoxicity and apoptosis by inhibition of ROS-mediated oxidative damage and regulation of ERK pathway, which validated its therapeutic potential in chemoprevention and chemotherapy of Aβ-induced neurotoxicity.

Keywords

Beta-amyloid Curcumin Apoptosis Neurotoxicity Oxidative damage 

Notes

Acknowledgments

The study was supported by the National Natural Science Foundation of China Nos. 81471212 and 81271275 to B.-L. Sun and No. 81501106 to C.-D. Fan; the Natural Science Foundation of Shandong ZR2015HQ009 to C.-D. Fan, ZR2015PH003 to X.-Y. Fu and ZR2014HM046 to Z.-C. Zheng.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that there is no conflict of interest.

Supplementary material

10571_2016_362_MOESM1_ESM.doc (83 kb)
Supplementary material 1 (DOC 83 kb)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Key Lab of Cerebral Microcirculation in Universities of ShandongTaishan Medical UniversityTaianChina
  2. 2.School of Basic MedicineTaishan Medical UniversityTaianChina
  3. 3.Departments of RehabilitationTaian Central HospitalTaianChina

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