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Fig. 5 | Molecular Neurodegeneration

Fig. 5

From: Neurotrophic factor small-molecule mimetics mediated neuroregeneration and synaptic repair: emerging therapeutic modality for Alzheimer’s disease

Fig. 5

P021 treatment reduces abnormal hyperphosphorylation of tau in 3xTg-AD mice. Reprinted from Kazim et al. [99] with permission from Elsevier. a-d In the subiculum and the CA1 regions of the hippocampus, AT8 (phospho-tau: pSer202, pThr 205) load was significantly reduced by P021 treatment in 3xTg-AD mice (both 15–16 month-old/6 months treatment group and 21–22 month-old/12 months treatment group). a Representative photomicrographs illustrating AT8 immunoreactivity in the different regions of hippocampus from the 15–16 month-old/6 months treatment group are shown. b The AT8 load was calculated as the percentage of area occupied by immunoreactive label. Quantification of the immunoreactivity is shown as mean ± S.E.M. from Tg-Vh (n = 7), and Tg-P021 (n = 7). c Representative photomicrographs illustrating AT8 immunoreactivity in the different regions of hippocampus from the 21–22 month-old/12 months treatment group are shown. d The AT8 load calculated as the percentage of area occupied by immunoreactive label is shown as mean ± S.E.M. from Tg-Vh (n = 6), and Tg-P021 (n = 6). e, f Western blot analyses of tau pathology in 21–22 month old (12 months treatment) group. P021 treatment significantly reduced abnormal hyperphosphorylation of tau at sites pSer396/pSer404 (PHF-1) and pSer262/pSer356 (12E8). Pan-tau antibody, R134d did not show any significant difference between groups. Blots developed with human specific tau antibody 43D showed the protein expression only in 3xTg-AD mice. Quantification of the Western blots is shown as mean ± S.E.M. from WT-Vh (n = 5), WT-P021 (n = 5), Tg-Vh (n = 6), and Tg-P021 (n = 7). *p < 0.05, **p < 0.01, and ***p < 0.001. Scale bar = 100 μm. WT-Vh = wild-type control mice treated with vehicle diet; WT-P021 = wild-type mice treated with P021 diet; Tg-Vh = 3xTg-AD mice treated with vehicle diet; Tg-P021 = 3xTg-AD mice treated with P021 diet

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