Everolimus (RAD001) ameliorates vascular cognitive impairment by regulating microglial function via the mTORC1 signaling pathway

RAD001 inhibited mTORC1 thereby decreasing the activity of P-p70S6k. Downregulated P-p70S6k then lost the feedback loop, leading to an increased activation of phosphatidyl inositol 3-kinase (PI3K). Afterward, active PI3K activated the prosurvival kinase, Akt, which then shifted microglia from the destructive M1 phenotype toward the beneficial M2 phenotype, thereby eliciting the protection of cholinergic neuron function. IRS-1, insulin receptor substrate 1.132