Fig 1: Varlitinib selectively diminishes tau phosphorylation in 6-month-old tau-overexpressing PS19 mice. (A, C, E) Six-month-old tau-overexpressing PS19 mice were injected with varlitinib (20 mg/kg, i.p.) or vehicle (5% DMSO, 10% PEG, 20% Tween-80, i.p.) daily for 14 days, and immunofluorescence staining was conducted with anti-AT100, anti-AT180, and anti-DYRK1A antibodies. (B, D, F) Quantification of data from (A, C, E) (n = 5 mice/group, AT100: Veh: 17 brain sections, Varlitinib: 21 brain sections; AT180: Veh: 17 brain sections, Varlitinib: 21 brain sections; DYRK1A: Veh: 17 brain sections, Varlitinib: 21 brain sections) * p < 0.05, *** p < 0.001. Veh, Vehicle. Scale bar=50 µm.
Fig 2: Varlitinib reduces tau hyperphosphorylation and tau kinase DYRK1A expression in 3-month-old tau-overexpressing PS19 mice. (A, C, E) Three-month-old tau-overexpressing PS19 mice were injected with varlitinib (20 mg/kg, i.p.) or vehicle (5% DMSO, 10% PEG, 20% Tween-80, i.p.) daily for 14 days, and immunofluorescence staining was conducted with anti-AT100, anti-AT180, and anti-DYRK1A antibodies. (B, D, F) Quantification of data from (A, C, E) (n = 11 mice/group, AT100: Veh: 40 brain sections, Varlitinib: 34 brain sections; AT180: Veh: 47 brain sections, Varlitinib: 42 brain sections; DYRK1A: Veh: 47 brain sections, Varlitinib: 42 brain sections, 2 experimental replicates per group). * p < 0.05, *** p < 0.001. Veh: Vehicle. Scale bar=50 μm.
Fig 3: (A) working model for how varlitinib alters LPS/tau-mediated neuroinflammatory responses and tauopathy in vivo. In the LPS-induced model of neuroinflammation in wild-type mice, varlitinib inhibits EGFR/HER2 and TLR4-linked NLRP3 inflammasome activation, leading to suppression of LPS-induced proinflammatory/neuroinflammatory responses. In tau-overexpressing PS19 mice, varlitinib inhibits tau kinase DYRK1A activation, resulting in downregulation of neuroinflammatory responses and tau pathology.
Fig 4: Lomerizine pretreatment significantly reduces LPS-mediated tau kinase DYRK1A and GSK3a/ß activation in the brain of wild-type mice. (A, E) Immunofluorescence staining of DYRK1A and GSK3a/ß in brain tissues from wild-type mice injected with vehicle (2% DMSO, i.p.) or lomerizine (20 or 30 mg/kg, i.p.) daily for 7 days followed by LPS (10 mg/kg, i.p.) or PBS. (B–D) Quantification of data from A (n = 18–20 brain slices from 5 mice/group). (F–H) Quantification of data from E (n = 17–26 brain slices from 5 mice/group). *p < 0.05, **p < 0.01, ***p < 0.001. (A) Scale bar = 200 µm, (E) Scale bar = 100 µm.
Supplier Page from Abcam for Anti-DYRK1A antibody - C-terminal