Reversal of BetaAmyloidInduced Neurotoxicity in

Authors: Cundong Fan Yuan Li Xiaoting Fu Qingjian Wu Yajun Hou Mingfeng Yang Jingyi Sun Xiaoyan Fu Zuncheng Zheng Baoliang Sun

Publish Date: 2016/03/14

Volume: 37, Issue: 2, Pages: 211-222

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Abstract

Progressive accumulation of betaamyloid 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 Aβinduced 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 Aβinduced neurotoxicity However the molecular mechanism remains elusive The present study evaluated the protective effect of Cur against Aβinduced cytotoxicity and apoptosis in PC12 cells and investigated the underlying mechanism The results showed that Cur markedly reduced Aβinduced cytotoxicity by inhibition of mitochondriamediated apoptosis through regulation of Bcl2 family The PARP cleavage caspases activation and ROSmediated 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 Aβinduced cytotoxicity and apoptosis by inhibition of ROSmediated oxidative damage and regulation of ERK pathway which validated its therapeutic potential in chemoprevention and chemotherapy of Aβinduced neurotoxicityThe study was supported by the National Natural Science Foundation of China Nos 81471212 and 81271275 to BL Sun and No 81501106 to CD Fan the Natural Science Foundation of Shandong ZR2015HQ009 to CD Fan ZR2015PH003 to XY Fu and ZR2014HM046 to ZC Zheng

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