fig3

Figure 3. Therapeutic pathways to mediate post-translational tau modifications. (A) GABAAR inhibitors bind to GABAAR to inhibit the hyperphosphorylation of tau^[22,35]. GSK-3β inhibitors likewise block tau hyperphosphorylation^[36-40]; (B) Acetylated tau exhibits lower levels of proteasomal degradation. SIRT1 promoters inhibit the acetylation of tau to enable pathologic tau degradation in the proteasome^[69-71]; (C) Upregulation of 5-HT4 promotes the ubiquitination of tau to promote proteasomal breakdown on pathologic tau^[69,72-74]; (D) Upregulation of O-GlcNAcase promotes the O-GlcNAcylation of tau to lower levels of tau hyperphosphorylation^[34,75-77]; (E) The drugs LMTM and ACI-3024 inhibit tau aggregation^[34,78-80]. Created with BioRender.com. GABAAR: γ-aminobutyric acid sub-type A receptor; GSK-3β: glycogen synthase kinase-3β; LMTM: leuco-methylthioninium bis(hydromethanesulphonate); SIRT1: Deacetylase protein sirtuin 1.