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在阿尔茨海默病小鼠模型中,他米巴罗汀通过抑制核因子κB介导的信号传导来降低β-分泌酶1(BACE1)的表达。

Reduction BACE1 expression via suppressing NF-κB mediated signaling by Tamibarotene in a mouse model of Alzheimer's disease.

作者信息

Qiao Aimin, Li Jieyi, Hu Yaohua, Wang Jinquan, Zhao Zizhuo

机构信息

Guangdong Province Key Laboratory for Biotechnology Drug Candidates and School of Bioscience and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China.

Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

出版信息

IBRO Neurosci Rep. 2021 Feb 14;10:153-160. doi: 10.1016/j.ibneur.2021.02.004. eCollection 2021 Jun.

Abstract

This present study examined the effect of Tamibarotene (AM80) in APP/PS1 mice, a well-established AD mouse model. AM80 was intraperitoneal administered to 3-month-old APP/PS1 mice at a dose of 5 mg/kg/day for 16 weeks. The results clearly showed that AM80 could reduce amyloid-β peptides through impact on APP processing and reduce microglia and astrocyte activation in APP/PS1 mice. The most notable finding in the present study was that inhibitory effect on BACE1 mediated by NF-κB pathway underlies the anti-inflammatory action of AM80. Moreover, AM80 could significantly decrease synaptic loss and enhance the expressions of Synapsin and Drebrin. Therefore, AM80 treatment may have the preclinical prevention of AD with new therapeutic strategies.

摘要

本研究检测了他米巴罗汀(AM80)对APP/PS1小鼠(一种成熟的阿尔茨海默病小鼠模型)的影响。将AM80以5毫克/千克/天的剂量腹腔注射给3个月大的APP/PS1小鼠,持续16周。结果清楚地表明,AM80可通过影响APP加工过程来减少淀粉样β肽,并减少APP/PS1小鼠中的小胶质细胞和星形胶质细胞活化。本研究最显著的发现是,AM80的抗炎作用的基础是其对由NF-κB途径介导的β-分泌酶1(BACE1)的抑制作用。此外,AM80可显著减少突触损失,并增强突触素和脑桥蛋白的表达。因此,AM80治疗可能为阿尔茨海默病的临床前预防提供新的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/776a/8019995/01d5f7d9080a/gr1.jpg

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