Caspase-3 short hairpin RNAs: a potential therapeutic agent in neurodegeneration of aluminum-exposed animal model.
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.
Qinli
Q
Zhang
Na
N
Li
Xia
X
Jiao
Xiujun
X
Qin
Ramanjit
R
Kaur
Xiaoting
X
Lu
Jing
J
Song
Linping
L
Wang
Junming
J
Wang
School of Public Health, Shanxi Medical University, Xin Jian Nan Lu 56, Taiyuan Shanxi 030001, China. zhangql9306111@gmail.com.
Qiao
Q
Niu
D000535:Aluminum / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D001362:Avoidance Learning; D053148:Caspase 3 / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000473:pathology; D004195:Disease Models, Animal; D005106:Exploratory Behavior; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D055785:Gene Knockdown Techniques / Q000379:methods; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology / Q000628:therapy*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D034741:RNA, Small Interfering / Q000627:therapeutic use*
D034741:RNA, Small Interfering; D000535:Aluminum; D053148:Caspase 3