Monitoring of Intracellular Tau Aggregation Regulated by OGA/OGT Inhibitors

Title
Monitoring of Intracellular Tau Aggregation Regulated by OGA/OGT Inhibitors
Authors
임성수마무눌 하크남길수류나연임혜원김윤경
Keywords
tau; glycosylation; aggregation; phosphorylation; OGA; OGT; neurodegeneration
Issue Date
2015-08
Publisher
International journal of molecular sciences
Citation
VOL 16, 20212-20224
Abstract
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.
URI
http://pubs.kist.re.kr/handle/201004/50656
ISSN
14220067
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KIST Publication > Article
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