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

[ Vol. 15 , Issue. 11 ]

Author(s):

Zhiyou Cai*, Chuanling Wang, Wenbo He and Yi Chen   Pages 1045 - 1052 ( 8 )

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.

Affiliation:

Department of Neurology, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing, 400013, Chongqing, Department of Neurology, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei Province, Department of Neurology, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei Province, Department of Neurology, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei Province



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