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RESEARCH AND REPORT ARTICLE: NEURODEGENERATIVE DISEASE AND NEURAL REGENERATION
Year : 2013  |  Volume : 8  |  Issue : 33  |  Page : 3095-3106

Targeting β-secretase with RNAi in neural stem cells for Alzheimer's disease therapy


Department of Neurobiology and Anatomy, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China

Correspondence Address:
Feng Li
Professor, Department of Neurobiology and Anatomy, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, Guangdong Province
China
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Source of Support: This work was supported by grants from the National Natural Science Foundation of China, No. 81271476, and the Natural Science Foundation of Guangdong Province, No. S2011010004366., Conflict of Interest: None


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There are several major pathological changes in Alzheimer's disease, including apoptosis of cholinergic neurons, overactivity or overexpression of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) and inflammation. In this study, we synthesized a 19-nt oligonucleotide targeting BACE1, the key enzyme in amyloid beta protein (Aβ) production, and introduced it into the pSilenCircle vector to construct a short hairpin (shRNA) expression plasmid against the BACE1 gene. We transfected this vector into C17.2 neural stem cells and primary neural stem cells, resulting in downregulation of the BACE1 gene, which in turn induced a considerable reduction in reducing Aβ protein production. We anticipate that this technique combining cell transplantation and gene therapy will open up novel therapeutic avenues for Alzheimer's disease, particularly because it can be used to simultaneously target several pathogenetic changes in the disease.


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