Skip to main content
Fig. 4 | Molecular Neurodegeneration

Fig. 4

From: Promoting tau secretion and propagation by hyperactive p300/CBP via autophagy-lysosomal pathway in tauopathy

Fig. 4

New p300 Inhibitor 37892 Reduces Tau Secretion (a) Structure of SMDC37892. b 37892 inhibited tau acetylation by p300 with an IC50 of 35 μM. c Concentration-response curve (CRC) for 37892, quantified from p300 activity in HEK293T cells. dg 37892 treatment in human iPSC-derived neurons. d Representative immunoblot of ac-tau (K174), t-tau, and GAPDH in lysates of human iPSC-induced neurons treated with DMSO (control) or 37892 (50 μM) for 3 days. Quantification of levels of ac-tau (e) and intracellular t-tau (f) after 3 days of treatment, normalized to control. g Quantification of tau secretion over 3 h, normalized to intracellular tau levels, and normalized to control. n = 6 wells from three independent experiments. *p < 0.05, ***p < 0.001 by unpaired t test. hj 37892 treatment increases autophagic flux in hTau-expressing mouse primary neurons. h Representative immunoblots of p62, LC3-II and actin in primary neurons treated with 37892 (50 μM), BafA1 (5 nM), or both, for 24 h. i Autophagic flux in control and 37892-treated neurons quantified from the increase of LC3-II levels in response to BafA1 treatment, normalized to control. n = 6 wells from three independent experiments. **p < 0.01 by unpaired t test. j Quantification of tau secretion over 3 h in p300/CBP double knockout neurons treated with 37892. p300F/F/CBPF/F primary neurons were infected with lenti-ctrl or lenti-Cre, and treated with DMSO (−) or 37892 (50 μM) for 24 h. n = 4 wells from 2 independent experiments. *p < 0.05, ns, non-significant, by one-way ANOVA and Sidak’s multiple comparisons test. Values are mean ± SEM

Back to article page
\