Caspase-3 Short Hairpin RNAs: A Potential Therapeutic Agent in Neurodegeneration of Aluminum-Exposed Animal Model

Author(s): Qinli Zhang, Na Li, Xia Jiao, Xiujun Qin, Ramanjit Kaur, Xiaoting Lu, Jing Song, Linping Wang, Junming Wang, Qiao Niu.

Journal Name: Current Alzheimer Research

Volume 11 , Issue 10 , 2014

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Abstract:

There is abundant evidence supporting the role of caspases in the development of neurodegenerative disease, including Alzheimer’s disease (AD). Therefore, regulating the activity of caspases has been considered as a therapeutic target. However, all the efforts on AD therapy using pan-caspase inhibitors have failed because of uncontrolled adverse effects. Alternatively, the specific knockdown of caspase-3 gene through RNA interference (RNAi) could serve as a future potential therapeutic strategy. The aim of the present study is to down-regulate the expression of caspase-3 gene using lentiviral vector-mediated caspase-3 short hairpin RNA (LV-Caspase-3 shRNA). The effect of LV-Caspase-3 shRNA on apoptosis induced by aluminum (Al) was investigated in primary cultured cortical neurons and validated in C57BL/6J mice. The results indicated an increase in apoptosis and caspase-3 expression in primary cultured neurons and the cortex ofmice exposed to Al, which could be down-regulated by LV-Caspase-3 shRNA. Furthermore, LV-Caspase-3 shRNA reduced neural cell death and improved learning and memory in C57BL/6J mice treated with Al. Our results suggest that LV-caspase-3 shRNA is a potential therapeutic agent to prevent neurodegeneration and cognitive dysfunction in aluminum- exposed animal models. The findings provide a rational gene therapy strategy for AD.

Keywords: Apoptosis, Alzheimer’s disease, caspase-3, lentiviral vector-mediated caspase-3 shRNA, RNA interference.

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Article Details

VOLUME: 11
ISSUE: 10
Year: 2014
Page: [961 - 970]
Pages: 10
DOI: 10.2174/1567205011666141107150938

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