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. 2021 Jun 2;12:3291. doi: 10.1038/s41467-021-23597-9

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© The Author(s) 2021, corrected publication 2021

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. 7 — a Treatment of SH-SY5Y cells with the proteasome inhibitor MG132 did not affect Tau degradation mediated by UBE4B/STUB1. b Treatment with chloroquine (CQ), an autophagy inhibitor, affected Tau degradation by UBE4B/STUB1. c Pepstatin A (PEPA) and E64D, autophagy inhibitors, inhibited Tau degradation by UBE4B/STUB1. All western blots were performed three times. d Schematic illustration of autophagy inhibitor injection to the dentate gyrus of Tau-BiFC mice. e Schematic illustration of the work flow for autophagy inhibitor injection and pathological examination in Tau-BiFC mice. f CQ and E64D plus PEPA (E64D + PEPA) increased pTau (S202/T205) levels in the dentate gyrus relative to saline-injected controls. GCL granular cell layer, POL polymorphic layer. g, h Densitometry analysis revealed that chloroquine and ED64 + PEPA significantly increased both pTau (S202/T205) and Tau-BiFC levels in the dentate gyrus relative to saline-injected controls (AAV-UBE4B + AAV-STUB1 (saline control), N = 4; CQ + AAV-UBE4B + AAV-STUB1, N = 4; E64D/PEPEA + AAV-UBE4B + AAV-STUB1, N = 4; N = 4 biologically independent animals). In the box plots the whiskers represent the 5th to 95th percentile range. i AAV-UBE4B and AAV-STUB1 decreased LC3 levels in the dentate gyrus relative to control. Scale bars (white): 40 μm. j AAV-UBE4B and AAV-STUB1 decreased p62 levels in the dentate gyrus relative to control. Scale bars (white): 40 μm. k Densitometry analysis revealed that autophagy inhibitors significantly increased LC3 levels in the dentate gyrus relative to control (AAV-Control, N = 4; AAV-UBE4B + AAV-STUB1, N = 4; CQ + AAV-UBE4B + AAV-STUB1, N = 4; E64D/PEPA + AAV-UBE4B + AAV-STUB1, N = 4; N = 4 biologically independent animals). In the box plots the whiskers represent the 5th to 95th percentile range. l Densitometry analysis revealed that autophagy inhibitors significantly increased p62 levels in the dentate gyrus relative to control (AAV-Control, N = 4; AAV-UBE4B + AAV-STUB1, N = 4; CQ + AAV-UBE4B + AAV-STUB1, N = 4; E64D/PEPA + AAV-UBE4B + AAV-STUB1, N = 4; N = 4 biologically independent animals). In the box plots the whiskers represent the 5th to 95th percentile range. Data are presented as means ± s.e.m. Statistical significance was determined with a two-tailed Student’s t-test. Statistical source data. Each exact p value was listed in Statistical source data.