Reduction of Aβ Generation by Schisandrin B through Restraining Beta-Secretase 1 Transcription and Translation.

Abstract:

:BACKGROUND Beta-secretase 1 (BACE1) is a rate-limiting enzyme in the generation of amyloid beta peptides, which are associated with Alzheimer's disease (AD). It has been reported that Schisandrin B could improve cognitive functions in animal models of AD, but the underlying mechanisms are not completely understood. MATERIAL AND METHODS In this research, in order to investigate the effects of Schisandrin B on amyloid-β (Aβ) metabolism and its mechanisms, amyloid precursor protein (APP) and its proteolytic products were determined by enzyme-linked immunosorbent assay (ELISA), western blotting, and RT-PCR after incubation of N2a/Swe cells with Schisandrin B. RESULTS The results indicated that Schisandrin B can significantly reduce the level of secretion of Aβ40 and Aβ42 secreted in N2a/Swe cells. Additionally, there was nonsignificant change in APP level after Schisandrin B treatment. Treatment of Schisandrin B dramatically reduced the mRNA and protein expression levels of BACE1. Moreover, Schisandrin B treatment resulted in a reduction of protein level of sAPPβ, an APP fragment cleavage by BACE1. CONCLUSIONS These results suggest that Schisandrin B inhibits the transcription and translation of BACE1, suppresses the activity of BACE1, and ultimately attenuates Aβ generation, which provides a novel mechanism for the regulation of Aβ metabolism by Schisandrin B.

journal_name

Med Sci Monit

authors

Li Z,Liu XC,Li R,Chang J

doi

10.12659/msm.905127

subject

Has Abstract

pub_date

2018-02-28 00:00:00

pages

1219-1224

eissn

1234-1010

issn

1643-3750

pii

905127

journal_volume

24

pub_type

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