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Figure 5. Immunomodulatory therapeutics to inhibit pathologic tau propagation. (A) Activating TREM2 with specific antibodies inhibits the hyperphosphorylation and aggregation of tau while also activating the PI3K/AKT/mTOR pathway to promote microglia survival^[122-125]; (B) KO of IκB Kinase inhibits the phosphorylation of IκB, thus preventing the NF-κB-driven hyperphosphorylation of tau^[126-128]; (C) Torin-1 and Digoxin promote the nuclear internalization and expression of TFEB in astrocytes, which promotes cellular uptake of tau and the proteasomal destruction of pathologic tau^[25,129,130]; (D) GLP1R agonists drive the inhibition of GSK-3β to prevent hyperphosphorylation and subsequent tau aggregation, while inhibiting the conversion of astrocytes to their proinflammatory phenotype^[131-133]. Created with BioRender.com. AKT: Protein kinase B; GLP1R: glucagon-like peptide-1 receptor; GSK-3β: glycogen synthase kinase-3β; KO: knockout; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; PI3K: phosphoinositide 3-kinase; TFEB: Transcription factor EB; TREM2: Triggering receptor expressed on myeloid cells 2.