O-GlcNAc modification differentially regulates microtubule binding and pathological conformations of tau isoforms in vitro.

ABSTRACT: Tau proteins undergo several posttranslational modifications in physiological and disease conditions. In Alzheimer's disease, O-GlcNAcylation modification of serine/threonine (S/T) residues in tau is reduced. In mouse models of tauopathy, O-GlcNAcase inhibitors lead to increased O-GlcNAcylation and decreased filamentous aggregates of tau. However, various nonfilamentous tau conformations, linked to toxicity and neurodegeneration in tauopathies, involve processes like oligomerization, misfolding, and greater exposure of the phosphatase-activating domain in the amino terminus of tau. Additionally, it is becoming clearer that posttranslational modifications may differently regulate tau pathobiology in an isoform-dependent manner. Therefore, it is crucial to investigate the effects of O-GlcNAc

SUBMITTER: Alhadidy MM 

PROVIDER: S-EPMC11927755 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature