Tetrahydroxystilbene glucoside modulates amyloid precursor protein processing via activation of AKT-GSK3β pathway in cells and in APP/PS1 transgenic mice

Journal Article · Mon Jan 15 04:00:00 EST 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2017.11.059· OSTI ID:23100619

Yin, Xiaomin ^[1]; Chen, Chen ^[1]; Xu, Ting ^[2]; Li, Lin; Zhang, Lan ^[1]

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1. Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Beijing Institute for Brain Disorders, Beijing Engineering Research Center for Nerve System Drugs, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, PR (China)
2. Department of Biochemistry and Molecular Biology, School of Medicine, Nantong University, Nantong, Jiangsu 226001, PR (China)

Alternative splicing of amyloid precursor protein (APP) exon 7 generates the isoforms containing a Kunitz protease inhibitor (KPI) domain. APP-KPI levels in the brain are correlated with amyloid beta (Aβ) production. Here, we determined the effect of Tetrahydroxystilbene glucoside (TSG) on the AKT-GSK3β pathway. We found GSK3β increased APP-KPI inclusion level and interacted with the splicing factor ASF. TSG was intragastrically administered to 5-month-old APP/PS1 transgenic mice for 12 months. We found that the activated the AKT-GSK3β signaling pathway suppressed APP-KPI inclusion. Moreover, TSG treatment attenuated amyloid deposition in APP/PS1 mice. This study demonstrates the neuroprotective effect of TSG on APP expression, suggesting that TSG may be beneficial for AD prevention and treatment.

• OSTI ID: 23100619
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 495; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BRAIN
EXONS
PHOSPHOTRANSFERASES
TRANSGENIC MICE