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BACE1 RNA interference improves spatial memory and attenuates A β burden in a streptozotocin‐induced tau hyperphosphorylated rat model
Author(s) -
Yu ChunJiang,
Liu Wei,
Chen HongYuan,
Wang Li,
Zhang ZhiRen
Publication year - 2014
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.3055
Subject(s) - hyperphosphorylation , senile plaques , streptozotocin , rna interference , tau protein , intracellular , blot , chemistry , neuroscience , alzheimer's disease , pharmacology , microbiology and biotechnology , biology , medicine , biochemistry , endocrinology , disease , rna , diabetes mellitus , phosphorylation , gene
Both senile plaques and intracellular neurofibrillary tangles are important pathological characteristics in Alzheimer's disease. However, the relationship between A β deposition and tau hyperphosphorylation is unknown. In this study, the increased levels of full‐length amyloid precursor protein (APP), APP C‐terminal fragment ( β ‐CTF) and BACE1 were found in streptozotocin‐induced tau hyperphosphorylation models by quantitative polymerase chain reaction, Western blotting and immunohistochemistry methods. In the previous studies, few strategies focusing on inhibiting β ‐secretase (BACE1) in a tau hyperphosphorylation model were utilized. Here, BACE1 RNAi was used to treat the streptozotocin‐induced tau hyperphosphorylation animal models. BACE1 RNAi treatment improved the behavioural ability of animal models and reduced the amount of A β 1‐40 and A β 1‐42, accompanied by decreasing the levels of BACE1 and β ‐CTF. Our results demonstrated that neurological defects and neurotoxic fragments, including A β and β ‐CTF, were eliminated by BACE1 RNAi in the tau hyperphosphorylated model, implying the efficiency and safety of BACE1RNAi treatment against Alzheimer's disease. Copyright © 2014 John Wiley & Sons, Ltd.