PTM can also affect tau activity by blocking phosphorylation by O-GlcNAcylation, which is the attachment of N-acetylglucosamine (GlcNAc) moieties to serine/threonine residues by O-GlcNAcase (OGA); this process can attenuate subsequent hyperphosphorylation by kinases. [42] In the human AD brain, levels of O-GlcNAcylation were found to be reduced 50% compared to healthy controls, and this inversely correlated with tau hyperphosphorylation, supporting OGA inhibition and increasing O-GlcNAcylation as a therapeutic mechanism [43].
