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

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

doi:10.1016/j.ibneur.2021.02.004

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

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

Authors

Aimin Qiao¹, Jieyi Li¹, Yaohua Hu¹, Jinquan Wang¹, Zizhuo Zhao²

Affiliations

¹ Guangdong Province Key Laboratory for Biotechnology Drug Candidates and School of Bioscience and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China.
² Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

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.

Keywords: AM80; Alzheimer’s disease; BACE1; Neuroinflammation; Synapse.