Berberine alleviates amyloid-beta pathology in the brain of APP/PS1 transgenic mice. - GreenMedInfo Summary
Berberine alleviates amyloid-beta pathology in the brain of APP/PS1 transgenic mice via inhibitingβ/γ-secretases activity and enhancing α-secretases.
Curr Alzheimer Res. 2018 Jul 1. Epub 2018 Jul 1. PMID: 29962345
Zhiyou Cai
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.
METHODS: 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 ofβ/γ-secretases, enhances α-secretases, and lowers the Aβ level in the hippocampus of AD mice, and improves Alzheimer's-like cognitive impairment.