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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• 作者：Cun-dong Fan ; Yuan Li ; Xiao-ting Fu ; Qing-jian Wu…
• 关键词：Beta ; amyloid ; Curcumin ; Apoptosis ; Neurotoxicity ; Oxidative damage
• 刊名：Cellular and Molecular Neurobiology
• 出版年：2017
• 出版时间：March 2017
• 年：2017
• 卷：37
• 期：2
• 页码：211-222
• 全文大小：
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Neurosciences; Cell Biology; Neurobiology;
• 出版者：Springer US
• ISSN：1573-6830
• 卷排序：37

文摘

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.