Monitoring of Intracellular Tau Aggregation Regulated by OGA/OGT Inhibitors
- Monitoring of Intracellular Tau Aggregation Regulated by OGA/OGT Inhibitors
- 임성수; 마무눌 하크; 남길수; 류나연; 임혜원; 김윤경
- tau; glycosylation; aggregation; phosphorylation; OGA; OGT; neurodegeneration
- Issue Date
- International journal of molecular sciences
- VOL 16, 20212-20224
- Abnormal phosphorylation of tau has been considered as a key pathogenic
mechanism inducing tau aggregation in multiple neurodegenerative disorders, collectively
called tauopathies. Recent evidence showed that tau phosphorylation sites are protected with
O-linked β-N-acetylglucosamine (O-GlcNAc) in normal brain. In pathological condition,
tau is de-glycosylated and becomes a substrate for kinases. Despite the importance of
O-GlcNAcylation in tau pathology, O-GlcNAc transferase (OGT), and an enzyme catalyzing
O-GlcNAc to tau, has not been carefully investigated in the context of tau aggregation. Here,
we investigated intracellular tau aggregation regulated by BZX2, an inhibitor of OGT. Upon
the inhibition of OGT, tau phosphorylation increased 2.0-fold at Ser199 and 1.5-fold at
Ser396, resulting in increased tau aggregation. Moreover, the BZX2 induced tau aggregation
was efficiently reduced by the treatment of Thiamet G, an inhibitor of O-GlcNAcase (OGA).
Our results demonstrated the protective role of OGT in tau aggregation and also suggest the
counter-regulatory mechanism of OGA and OGT in tau pathology.
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