Berberine Alleviates Amyloid-Beta Pathology in the Brain of APP/PS1 Transgenic Mice via Inhibiting β/γ-Secretases Activity and Enhancing α-Secretases

Author(s): Zhiyou Cai*, Chuanling Wang, Wenbo He, Yi Chen.

Journal Name: Current Alzheimer Research

Volume 15 , Issue 11 , 2018

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Abstract:

Background: Berberine (BBR) has neuroprotective effects on many brain diseases, including Alzheimer’s disease (AD). Amyloid -beta (Aβ) senile plaque is the most classical pathological hallmarks of AD. Aβ produces from a sequential cleavage by β-secretase (beta-site amyloid precursor protein cleaving enzyme 1, BACE1) and γ -secretase. The aim of our work was to investigate whether the neuroprotective effects of BBR on AD is related to inhibiting Aβ pathology.

Method: The cognitive function of mice was assessed by the Morris water maze (MWM) test. The Aβ levels were determined by enzyme linked immunosorbent assay; the expression of APP, sAPPα, ADAM10 and ADAM17, sAPPβ and BACE1 was detected by Western blotting; and the activity of γ -secretase complex (NCT, PS1, Aph-1α and Pen-2) was determined by Western blotting and immunohistochemistry.

Results: BBR improved learning and memory deficits of APP/PS1 mice. BBR decreased Aβ levels in the hippocampus of APP/PS1 mice. BACE1 and sAPP -β levels in the BBR-treated groups were significantly reduced in the hippocampus of AD mice. BBR markedly decreased the expression of PS1, Aph-1α and Pen-2, but had no effect on NCT. The levels of sAPPα, 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 β/γ-secretases, enhances α-secretases, and lowers the Aβ level in the hippocampus of AD mice, and improves Alzheimer’s-like cognitive impairment.

Keywords: Berberine, cognitive dysfunction, amyloid-beta, β-secretase, γ-secretase, neurodegeneration.

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Article Details

VOLUME: 15
ISSUE: 11
Year: 2018
Page: [1045 - 1052]
Pages: 8
DOI: 10.2174/1567205015666180702105740
Price: $58

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