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The effect of BACE1-AS on β-amyloid generation by regulating BACE1 mRNA expression

Li, Fan, Wang, Yun, Yang, Hui, Xu, Yingying, Zhou, Xiaoyan, Zhang, Xiao, Xie, Zhaohong, Bi, Jianzhong·2019·BMC Molecular Biology
DOI 10.1186/s12867-019-0140-0PMC PMC6771094
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Abstract

Background: The BACE1 antisense transcript (BACE1-AS) is a conserved long noncoding RNA (lncRNA). The level of BACE1-AS is significantly increased and the level of the BACE1 mRNA is slightly increased in subjects with AD. BACE1-AS exerts a significant moderating effect on the expression of the BACE1 mRNA and promotes the formation of Aβ. After the administration of Aβ 1-42 to SH-SY5Y cells and C57/BL6J mice, we detected the expression of BACE1-AS, BACE1 mRNA, and BACE1 protein, as well as the concentration of Aβ 1-40. Then, we silenced the expression of BACE1-AS in SH-SY5Y and 20E2 cells using siRNAs targeting BACE1-AS and detected its effects on the levels of the BACE1 mRNA and BACE1 protein and Aβ 1-40 generation. Results: The administration of Aβ 1-42 increased the expression of BACE1-AS, BACE1 mRNA and protein, as well as the concentration of Aβ 1-40 in SH-SY5Y cells and the brains of C57BL/6J mice. Pretreatment with the BACE1-AS siRNA inhibited the effect of Aβ 1-42 on increasing the expression of BACE1-AS and BACE1, as well as the generation of Aβ. Conclusions: The mechanism by which exogenous Aβ 1-42 induces BACE1 expression and Aβ generation is mediated by BACE1-AS. BACE1-AS is involved in the mechanism regulating BACE1 expression and Aβ generation in APPsw transgenic cells.

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  • The action of BACE1-AS has been implicated in AD pathology, with increased BACE-AS in turn increasing BACE1 and Aβ-42.

    “The action of BACE1‐AS has been implicated in AD pathology, with increased BACE‐AS in turn increasing BACE1 and Aβ‐42.”

    From BACE1: More than just a β‐secretase (2022) · cites this paper as [64]

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Metadata

Authors
Li, F., Wang, Y., Yang, H., Xu, Y., Zhou, X., Zhang, X., Xie, Z., & Bi, J.
Venue
BMC Molecular Biology
Publisher
Springer Science and Business Media LLC
Published
2019-10-01
Volume
20
Issue
1
ISSN
1471-2199
DOI
10.1186/s12867-019-0140-0
PMC
PMC6771094
Cited by
52
References
1
Language
en
Licence
Funders
  • Natural Science Foundation of China (81870848)
  • Key Research and Development Program of Shandong Province (2017GSF218036, 2017GSF218046)

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