Fig. 4: sTREM2 attenuates tau phosphorylation by blocking the RhoA/ROCK pathway.

a Schematic illustration of the potential mechanism by which sTREM2 regulates tau phosphorylation: sTREM2 secreted from microglia binds neuronal TG2 and inactivates the RhoA/ROCK/GSK3β pathway, attenuating tau hyperphosphorylation. b, c Western blots showing the phosphorylation of tau and GSK3β in HEK293-Tau cells treated with control (Fc, 20 nM), Fc-sTREM2 (20 nM), or Tat-C3 (RhoA inhibitor, 0.1 μg/mL) for 24 h. d, e Western blots showing the phosphorylation of tau and GSK3β in HEK293-Tau cells treated with control (Fc, 20 nM), Fc-sTREM2 (20 nM), or Y-27632 (ROCK inhibitor) for 24 h. f, g Western blots showing the phosphorylation of tau and GSK3β in HEK293-Tau cells treated with control (Fc, 20 nM), Fc-sTREM2 (20 nM) for 24 h and incubated with RhoA activator (1 U/ml) or solvent for another 30 min. EK293-Tau cells were pretreated with control siRNA (si-NC), si-RhoA (h, i), or si-ROCK (j, k), and then treated with control (Fc, 20 nM) or Fc-sTREM2 (20 nM). Shown are the phosphorylation of tau and GSK3β (mean ± s.e.m.; one-way ANOVA for (c, e, g), two-way ANOVA for (i, k), n = 4 independent experiments; compared with the control group, *P < 0.05, **P < 0.01, ***P < 0.001).