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Lentivirus-mediated APP695-RNAi reduces apoptosis in APP transgenic mouse neurons

Zhao, Xinyua; Wen, Lijuna; Li, Guodongb; Ba, Qinghuac; Cui, Yuemeic; Han, Zhiqianga; Jia, Yanjiea; Xu, Yuminga

doi: 10.1097/WNR.0b013e32834b6c92
MOLECULAR NEUROSCIENCE
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Amyloid-β peptide (Aβ) is a cleavage product of the amyloid precursor protein (APP), which is thought to be important in the pathogenesis of Alzheimer's disease (AD). Recent evidence suggests that Aβ induces neuronal apoptosis in the brain and in primary neuronal cultures. If decreased Aβ whether could reduce the neuronal apoptosis? In this study, APP695-siRNA was delivered to hippocampal and cortical neurons of APP695 transgenic mice (AD model) in vitro using a recombinant lentivirus vector. The results show that lentivirus-mediated RNA interference of the APP695 gene could reduce neuronal apoptosis, possibly through the reduction of caspase-3 activity and the neuronal apoptosis pathway. These results suggest that lentivirus-mediated RNA interference may be a potential therapeutic for AD.

aDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University

bExperimental Center for Medicine, Zhengzhou University

cDepartment of Neurology, People's Hospital of Zhengzhou, Zhengzhou, Henan Province, China

Correspondence to Dr Yuming Xu, MD, PhD, Department of Neurology, The First Affiliated Hospital of Zhengzhou University, No. 1, East Jian She Road, Zhengzhou, Henan Province 450052, China Tel: +86 1383 8117 750; fax: +86 371 66975140; e-mail: Shenjingneike38@yahoo.cn

Received May 28, 2011

Accepted July 25, 2011

© 2011 Lippincott Williams & Wilkins, Inc.