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

Abstract:

: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.

journal_name

Neural Regen Res

authors

Liu Z,Li S,Liang Z,Zhao Y,Zhang Y,Yang Y,Wang M,Li F

doi

10.3969/j.issn.1673-5374.2013.33.003

subject

Has Abstract

pub_date

2013-11-25 00:00:00

pages

3095-106

issue

33

eissn

1673-5374

issn

1876-7958

pii

NRR-8-3095

journal_volume

8

pub_type

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