kinase 1  (Proteintech)

Journal: Journal of Neuroinflammation

Article Title: Dual inhibition of IRAK1/TAK1 signaling in astrocytes reduces accelerated mortality in human APOE4 knock-in APPswe/PSEN1dE9/P301S-Tau triple transgenic mouse model

doi: 10.1186/s12974-025-03564-7

Figure Lengend Snippet: Anserine inhibited TAK1- and IRAK1-mediated NF-κB activation in cultured astrocytes. A Schematic overview and representative images of the experimental design used to evaluate the effect of the natural anti-inflammatory dipeptide anserine on astrocyte activation. MSP-1 astrocytes were differentiated from neural stem-like MSP-1 cells by stimulation with CNTF and LIF for 5 days in vitro (scale bar, 50 μm). Astrocyte activation was induced by TNF-α or IL-1β (100 ng/ml, 24 h), confirmed by increased nuclear p-p65 immunoreactivity (scale bar, 10 μm). To study the effects of anserine on NF-κB activation, TNF-α or IL-1β stimulation was performed for 30 min. Anserine was administered before the stimulation. Except for C3 ELISA ( D and E ), anserine was used at 10 mM for all experiments. B and C In vitro kinase activity curves of TAK1-Table 1 ( B ) and IRAK1 ( C ) treated with L-anserine. D Quantification of C3 concentration in culture medium of Sham, IL-1β and IL-1β + Ans (0.8, 2, 10, and 50 mM) groups ( n = 6–8), with comparisons made versus the IL-1β group. E Quantification of C3 concentration in culture medium of Sham, TNF-α and TNF-α + Ans (0.8, 2, 10, and 50 mM) groups ( n = 6–8), with comparisons made versus the TNF-α group. F Quantification of nuclear p-p65 intensity of Sham, IL-1β and IL-1β + Ans (10 mM) groups ( n = 116–140), with comparisons made versus the IL-1β group. G Quantification of nuclear p-p65 intensity of Sham, TNF-α and TNF-α + Ans (10 mM) groups ( n = 103–109), with comparisons made versus the TNF-α group. H Quantification of p-IRAK1 fluorescence intensity in Sham, IL-1β and IL-1β + Ans (10 mM) groups ( n = 42–50), with comparisons made versus the IL-1β group. I Quantification of p-IRAK1 fluorescence intensity Sham, TNF-α and TNF-α + Ans (10 mM) groups ( n = 39–52), with comparisons made versus the TNF-α group. J Quantification of p-TAK1 fluorescence intensity in Sham, IL-1β and IL-1β + Ans (10 mM) groups ( n = 34–44), with comparisons made versus the IL-1β group. K Quantification of p-TAK1 fluorescence intensity in Sham, TNF-α and TNF-α + Ans (10 mM) groups ( n = 52–54), with comparisons made versus the TNF-α group. L GSEA of the Hallmark “TNF-α signaling via NF-κB” gene set. Ans, Anserine. M Volcano plots of differentially expressed genes (DEGs) (|log₂ fold change| >0.5, p < 0.05): left, TNF-α vs. Sham; right, TNF-α + Ans vs. TNF-α. Up-regulated genes are shown in red and down-regulated genes are shown in blue. Data are presented as mean ± SEM ( D and E ) or presented in violin plots ( F–K ) (median: bold dashed line; quartiles (1/4 and 3/4: dashed lines)) and were analyzed by one-way ANOVA with Dunnett’s multiple comparisons test ( D and E) or Kruskal-Wallis test with Dunn’s multiple comparisons test ( F–K ). All comparisons were made versus the TNF-α group in TNF-α–stimulated MSP-1 astrocytes or the IL-1β group in IL-1β–stimulated MSP-1 astrocytes. ** p < 0.01, **** p < 0.0001. Some elements in panel A were created with BioRender.com

Article Snippet: The potential targets of anserine within the NF-κB signaling pathway, including IKK-α, IKK-β, IRAK1, IRAK4, and TAK1-TAB1 were identified using an activity-based biochemical screening/profiling assay (CARNA BIOSCIENCES, Kobe, Japan).

Techniques: Activation Assay, Cell Culture, In Vitro, Enzyme-linked Immunosorbent Assay, Activity Assay, Concentration Assay, Fluorescence

Journal: Journal of Neuroinflammation

Article Title: Dual inhibition of IRAK1/TAK1 signaling in astrocytes reduces accelerated mortality in human APOE4 knock-in APPswe/PSEN1dE9/P301S-Tau triple transgenic mouse model

doi: 10.1186/s12974-025-03564-7

Figure Lengend Snippet: Graphical summary of this study. A Schematic illustration of the impact of Aβ pathology on the P301S tauopathy model. Aβ enhances the activation of A1 astrocytes, which in turn accelerates tau pathology and exacerbates tau-associated neurodegeneration in both immature and mature hippocampal neurons. Together, these pathological processes contribute to the accelerated mortality observed around 6.5 months of age. B Schematic illustration of the proposed mechanism by which anserine inhibits A1 astrocyte activation to prevent accelerated mortality in E4-3Tg and TE4 mice. In the AD environment, astrocytes are activated by Aβ or pro-inflammatory cytokines via the corresponding receptors. Anserine is actively taken up by astrocytes via PEPT2 and inhibits NF-κB activation mediated by IRAK1 and TAK1 signaling. This inhibition reduces the production of pro-inflammatory cytokines such as C3, TNF-α, IL-1β, and C1q. Inhibited astrocytic C3 production alleviates tau-associated neurodegeneration. Moreover, decreased secretion of pro-inflammatory cytokines limits further A1 astrocyte activation. Together, these effects mitigate neurodegeneration, protect against cognitive decline, and reduce mortality. Elements in panel A and B were created with BioRender.com

Article Snippet: The potential targets of anserine within the NF-κB signaling pathway, including IKK-α, IKK-β, IRAK1, IRAK4, and TAK1-TAB1 were identified using an activity-based biochemical screening/profiling assay (CARNA BIOSCIENCES, Kobe, Japan).

Techniques: Activation Assay, Inhibition