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

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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.

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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.

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    Authors and Affiliations

    1. Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China

      Cun-dong Fan, Yuan Li, Xiao-ting Fu, Qing-jian Wu, Ya-jun Hou, Ming-feng Yang & Bao-liang Sun

    2. School of Basic Medicine, Taishan Medical University, Taian, 271000, Shandong, China

      Jing-yi Sun & Xiao-yan Fu

    3. Departments of Rehabilitation, Taian Central Hospital, Taian, 271000, Shandong, China

      Zun-cheng Zheng

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    1. Cun-dong Fan
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    Cun-dong Fan, Yuan Li and Xiao-ting Fu have contributed equally to this work.

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    Fan, Cd., Li, Y., Fu, Xt. et al. Reversal of Beta-Amyloid-Induced Neurotoxicity in PC12 Cells by Curcumin, the Important Role of ROS-Mediated Signaling and ERK Pathway. Cell Mol Neurobiol 37, 211–222 (2017). https://doi.org/10.1007/s10571-016-0362-3

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