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. 2014 Dec 16;4(12):e489. doi: 10.1038/tp.2014.132

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Copyright © 2014 Macmillan Publishers Limited

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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The effect of tetrahydrocarbazoles on APP processing. (a) Relative Aβ38, Aβ40 and Aβ42 levels, decreased after 16 h treatment with synthesized tetrahydrocarbazoles at 10 μM in HEK293 cells coexpressing APPsw and PS1-M146L. Sulindac sulfide (50 μM), a γ-secretase modulator, and DAPT (10 μM), a γ-secretase inhibitor, were used as positive controls. Inside the box, a schematic illustration of APP processing by α-, β- and γ-secretase is presented. (b) Relative Aβ42/Aβ40 ratios calculated from a. Treatment with the majority of tetrahydrocarbazoles does not alter Aβ42/Aβ40 ratio, whereas positive control Sulindac sulfide significantly lowers Aβ42/Aβ40 ratio. (c) Relative Aβ38, Aβ40 and Aβ42 levels are decreased after 16 h treatment with select tetrahydrocarbazoles at 10 μM in HEK293 cells overexpressing wild-type APP. (d) Relative Aβ42/Aβ40 ratios calculated from c. Treatment with select tetrahydrocarbazoles tested does not alter Aβ42/Aβ40 ratio. (e) Relative sAPPα and sAPPβ levels after 16 h compound treatment in wild-type HEK293 cells. Treatment with select tetrahydrocarbazole derivatives does not (or only marginally) affect secreted sAPPα levels, whereas secreted sAPPβ fragment levels are remarkably decreased. All the values are normalized to the value of DMSO, which is set to 1. (n.s., non-significant; *P<0.05, **P<0.01 and ***P<0.001; n=2). APP, amyloid precursor protein; DMSO, dimethyl sulfoxide; PS1, presenilin 1.