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. 2021 Mar 15;18:71. doi: 10.1186/s12974-021-02121-2

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© The Author(s) 2021

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 3 — Jagged-1/Notch signaling and regulation in the context of BACE1 activity. A cell that is sending (top) a Notch signal to a receiving cell (Bottom) via notch ligand Jag1. (1) Notch/Jag1 binding causes a conformational change in Notch1 which results in subsequent cleavages, resulting in the release of the intracellular domain of Notch (NCID) to relocate to the nucleus and activate downstream signaling. (2) Notch signaling can be regulated by binding Jag1 on the surface of the receiving cell. (3) BACE1 can regulate Notch1 signaling via the cleavage of Jag1. This cleavage can have different effects depending on whether it is taking place on a receiving cell or sending cell. In the sending cell, BACE1 activity results in reduced Jag1 available for signaling. In the receiving cell BACE1 activity results in increased Notch1 signaling by reducing the amount of cis-regulating Jag1