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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.
Curr Alzheimer Res 2018; 15(11):1045-1052CA

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.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29962345

Citation

Cai, Zhiyou, et al. "Berberine Alleviates Amyloid-Beta Pathology in the Brain of APP/PS1 Transgenic Mice Via Inhibiting β/γ-Secretases Activity and Enhancing Α-Secretases." Current Alzheimer Research, vol. 15, no. 11, 2018, pp. 1045-1052.
Cai Z, Wang C, He W, et al. Berberine Alleviates Amyloid-Beta Pathology in the Brain of APP/PS1 Transgenic Mice via Inhibiting β/γ-Secretases Activity and Enhancing α-Secretases. Curr Alzheimer Res. 2018;15(11):1045-1052.
Cai, Z., Wang, C., He, W., & Chen, Y. (2018). Berberine Alleviates Amyloid-Beta Pathology in the Brain of APP/PS1 Transgenic Mice via Inhibiting β/γ-Secretases Activity and Enhancing α-Secretases. Current Alzheimer Research, 15(11), pp. 1045-1052. doi:10.2174/1567205015666180702105740.
Cai Z, et al. Berberine Alleviates Amyloid-Beta Pathology in the Brain of APP/PS1 Transgenic Mice Via Inhibiting β/γ-Secretases Activity and Enhancing Α-Secretases. Curr Alzheimer Res. 2018;15(11):1045-1052. PubMed PMID: 29962345.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Berberine Alleviates Amyloid-Beta Pathology in the Brain of APP/PS1 Transgenic Mice via Inhibiting β/γ-Secretases Activity and Enhancing α-Secretases. AU - Cai,Zhiyou, AU - Wang,Chuanling, AU - He,Wenbo, AU - Chen,Yi, PY - 2018/01/17/received PY - 2018/04/10/revised PY - 2018/06/29/accepted PY - 2018/7/3/pubmed PY - 2019/10/18/medline PY - 2018/7/3/entrez KW - Berberine KW - amyloid-beta KW - cognitive dysfunction KW - neurodegeneration KW - β-secretase KW - γ-secretase. SP - 1045 EP - 1052 JF - Current Alzheimer research JO - Curr Alzheimer Res VL - 15 IS - 11 N2 - 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. SN - 1875-5828 UR - https://www.unboundmedicine.com/medline/citation/29962345/Berberine_Alleviates_Amyloid_Beta_Pathology_in_the_Brain_of_APP/PS1_Transgenic_Mice_via_Inhibiting_β/γ_Secretases_Activity_and_Enhancing_α_Secretases_ L2 - http://www.eurekaselect.com/163383/article DB - PRIME DP - Unbound Medicine ER -