Fig. 4: PQBP1–cGAS–STING pathway mediates Tau-induced NFκB activation in microglia.

a Protocol of tamoxifen-induced Pqbp1 knockout in primary microglia prepared from newborn Pqbp1-cKO mice. WB western blot. b Effect of PQBP1 deficiency, cGAS knockdown, and STING knockdown on Tau 410/441-induced nuclear translocation of NFκB in microglia. Activated microglia with nuclear NFκB are indicated with red arrows. Non-activated microglia are indicated with white arrows. Images were obtained by confocal microscopy. c Quantitative analyses of % nuclear NFκB-positive microglia in six visual fields in normal condition, PQBP1 deficiency, cGAS knockdown, and STING knockdown. N = 6 (visual fields). ^##P < 0.01 in Tukey’s HSD test (vs non-induced Pqbp1-cKO). d Western blots reveal activation of NFκB (pSer536-p65) and IRF3 (pSer396-IRF3) after culture with non-polymerized Tau 410/441 in normal microglia, but not in tamoxifen-induced Pqbp1-cKO, siRNA-mediated cGAS-KD, or siRNA-mediated STING-KD microglia. This experiment was repeated independently, three times, with similar results. e Effect of PQBP1 depletion on microglia migration. FBS fetal bovine serum. N = 4 wells. Statistical test: Student’s t-test (two-sided). f Effect of PQBP1 depletion on microglia phagocytosis by using FITC-beads. AU arbitrary unit. N = 4 wells. For statistical analysis, a Student’s t-test (two-sided) was performed. Box plots show the median, quartiles, and whiskers that represent data outside the 25th to 75th percentile range.