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Fig. 1 | Alzheimer's Research & Therapy

Fig. 1

From: Selective suppression of the α isoform of p38 MAPK rescues late-stage tau pathology

Fig. 1

SB239063 and MW181 reduce inflammation-induced hyperphosphorylation of tau, p38α MAPK, and ATF2 activation in primary neurons. a Schematic showing 30-min pretreatment of 21 DIV Cx3cr1 +/+ primary cortical neurons with MW181 (2 μM), SB239063 (100 μM), or vehicle (Veh) followed by treatment with 25% Cx3cr1 –/– microglial conditioned media (CM) for 90 min prior to biochemical analysis of neuronal lysates. b, c Structural formulae of SB239063 (adapted from [68]) and MW181 (adapted from [26]). d, e Cx3cr1 –/– microglial CM significantly induced tau phosphorylation on AT8 and AT180 sites. Pretreatment of neurons with SB239063 or MW181 significantly reduced CM-induced tau phosphorylation on AT8 and AT180 sites. Quantifications are shown in e (n = 3 independent cultures, mean ± SEM of integrated density value (IDV) ratios as labeled. *p < 0.05; ***p < 0.001; one-way ANOVA with Tukey’s multiple comparison test). fi MW181 (f) or SB239063 (g) neuronal treatment showing reduction in the activated p-p38α MAPK (pT180/pY182) and AT8 site tau phosphorylation with a maximum reduction at 60 and 90 min time points (for MW181), and at 20 and 60 min time points (for SB239063) post CM treatment, which was considered as 0 min. Quantifications are shown in h (for MW181) and i (for SB239063). N = 3 independent cultures, mean ± SEM of IDV ratios as labeled. j, k Elevated levels of phosphorylated ATF2 (pT71) at 90 min after Cx3cr1 –/– microglial CM treatment. The pATF2 level was reduced by 30-min pretreatment with SB239063 and MW181. Quantifications are shown in k (n = 3 independent cultures, mean ± SEM of IDV ratios of pATF2/GAPDH; **p < 0.01; ***p < 0.001; one-way ANOVA with Tukey’s multiple comparison test)

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