期刊
CURRENT ALZHEIMER RESEARCH
卷 15, 期 11, 页码 1045-1052出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1567205015666180702105740
关键词
Berberine; cognitive dysfunction; amyloid-beta; beta-secretase; gamma-secretase; neurodegeneration
资金
- Chongqing Health and Family Planning Scientific Research Project [ZY201702042]
- Nature Science Foundation of Chongqing General Hospital
Background: Berberine (BBR) has neuroprotective effects on many brain diseases, including Alzheimer's disease (AD). Amyloid -beta (A beta) senile plaque is the most classical pathological hallmarks of AD. A beta produces from a sequential cleavage by beta-secretase (beta-site amyloid precursor protein cleaving enzyme 1, BACE1) and gamma-secretase. The aim of our work was to investigate whether the neuroprotective effects of BBR on AD is related to inhibiting A beta pathology. Method: The cognitive function of mice was assessed by the Morris water maze (MWM) test. The A beta levels were determined by enzyme linked immunosorbent assay; the expression of APP, sAPP alpha, ADAM10 and ADAM17, sAPP beta and BACE1 was detected by Western blotting; and the activity of gamma-secretase complex (NCT, PS1, Aph-1 alpha and Pen-2) was determined by Western blotting and immunohisto chemistry. Results: BBR improved learning and memory deficits of APP/PS1 mice. BBR decreased A beta levels in the hippocampus of APP/PS1 mice. BACE1 and sAPP-beta levels in the BBR-treated groups were significantly reduced in the hippocampus of AD mice. BBR markedly decreased the expression of PS1, Aph-1 alpha and Pen-2, but had no effect on NCT. The levels of sAPP alpha, ADAM10 and ADAM17 in the hippocampus of BBR-treated mice significantly increased, compared with the control ones (P<0.05). Conclusion: BBR inhibits the activity of beta/gamma-secretases, enhances a-secretases, and lowers the A beta level in the hippocampus of AD mice, and improves Alzheimer's-like cognitive impairment.
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