Monitoring of Intracellular Tau Aggregation Regulated by OGA/OGT Inhibitors

International Journal of Molecular Sciences

Sungsu Lim¹  Md. Mamunul Haque¹  Ghilsoo Nam¹  Nayeon Ryoo²  Hyewhon Rhim²  Yun Kyung Kim¹ 

[1] Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 136-791, South Korea; E-Mails:;Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 136-791, South Korea; E-Mail:

关键词: tau protein;    O-GlcNAcylation;    O-GlcNAc transferase;    O-GlcNAcase;    tau phosphorylation;    tau aggregation;   

DOI  :  10.3390/ijms160920212

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.