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. 2019 Dec 6;4:58. doi: 10.1038/s41392-019-0091-4

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© The Author(s) 2019

Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — MKP-1 inhibited APP processing through inactivation of the ERK/MAPK signaling pathway. a–e Immunoblot of the expression of MKP-1 b, P-ERK c, P-JNK d and P-P38 e in lysates of N2A^APP cells after overexpression of MKP-1 by LV_MKP-1 or knockdown of MKP-1 by LV_shMKP-1. *p < 0.05 and ***p < 0.001 by one-way ANOVA. n = 4–5 in each group. f–j Immunoblot of the expression of APP g, C89 h, C99 i and BACE1 j in lysates of N2A^APP cells treated with the ERK inhibitor U0126, the JNK inhibitor SP600125, the P38 inhibitor SB203580 or the three inhibitors together (Combined). *p < 0.05, **p < 0.01 and ***p < 0.001 by one-way ANOVA. n = 5–7 in each group. k, l The mRNA levels of human APP k and BACE1 l assessed by qPCR in N2A^APP cells and N2A^APP cells treated with U0126. ***p < 0.001 for APP and *p = 0.032 for BACE1 by unpaired Student’s t test. n = 3–4 in each group. m, n The promoter activity of APP m and BACE1 n assessed by luciferase assay in N2A^APP cells and N2A^APP cells treated with U0126. *p = 0.036 for APP and *p = 0.040 for BACE1 by unpaired Student’s t test. n = 3–4 in each group. o, p The degradation of APP o and BACE1 p as assessed by half-life measurements in the N2A^APP cells after U0126 treatment. p = 0.264 for APP and p = 0.847 for BACE1 by two-way ANOVA. n = 4–5 in each group.