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Fig. 3 | Acta Neuropathologica Communications

Fig. 3

From: Small-molecule modulation of the p75 neurotrophin receptor inhibits a wide range of tau molecular pathologies and their sequelae in P301S tauopathy mice

Fig. 3

LM11A-31 reduces tau misfolding and aggregation. a Western analyses of soluble hippocampal lysates performed with tau D1M9X antibody for total tau. bd Densitometric quantitation of bands in the indicated size ranges with p-values for the indicated comparisons shown. Statistical significance was determined using ANOVA with post hoc Sidak’s multiple comparison testing; n = 6–11 mice per group with two independent western analyses averaged per animal. e Western blot analysis of sarkosyl-insoluble lysates with D1M9X antibody. Over-exposed image demonstrates signal at < 50 and > 75 kDa, as well as at ~ 55 and ~ 68/64 kDa. Lower exposures were used for quantitation of ~ 68/64 kDa bands (Additional file 3: Fig. S3). fi Densitometric quantitation of bands at the indicated size ranges with p-values indicated. Statistical significance was determined using ANOVA with post hoc Sidak’s testing (f, h, i) or Kruskal–Wallis with post hoc Dunn’s testing multiple comparison testing (g); n = 6–11 mice per group with two independent western analyses averaged per animal. j Western blot analysis of hippocampal sarkosyl-insoluble lysates performed with HT7 antibody specific to human total tau. Over-exposed image demonstrates signal at > 75 kDa. Lower exposures were used for quantitation of ~ 68/64 kDa bands (Additional file 3: Fig. S3). k Densitometric analysis of the ~ 64 kDa signal with p-values indicated. Statistical significance was determined using ANOVA with post hoc Sidak’s multiple comparison testing; n = 6 mice per group with two independent western analyses averaged per animal. l, m Western blot analyses of hippocampal sarkosyl-insoluble lysates performed with the indicated antibodies. n, o Densitometric analysis of immunoblots (MC1, ~ 64 kDa; PHF-1, 68/64 kDa bands combined) with p-values indicated. Statistical significance was determined using Kruskal–Wallis with post hoc Dunn’s testing (n) or ANOVA with Sidak’s post hoc multiple comparison testing (o); n = 6–11 mice per group, with two independent western blots averaged per animal. p, q Western blot analyses of soluble hippocampal synaptosome lysates performed with the indicated antibodies. Bands at ~ 45 kDa in all four lanes (q) are due to prior probing of blots with actin antibody and persistence of signal. r, s Densitometric analysis of immunoblots blots (~ 64 kDa for MC1 or ~ 68 kDa for PHF-1) with p-values indicated. Statistical significance was determined using Kruskal–Wallis with post hoc Dunn’s testing; n = 6–11 mice per group with two independent western blots average per mouse. t ThioS hippocampal staining in 9-month old mice. u Quantification of hippocampal ThioS-positive staining. Statistical significance was determined using Kruskal–Wallis with post hoc Dunn’s testing; n = 8–13 mice per group

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