Lim, Sungsu Haque, Md. Mamunul Nam, Ghilsoo Ryoo, Nayeon Rhim, Hyewhon Kim, Yun Kyung 2024-01-20T06:04:26Z 2024-01-20T06:04:26Z 2022-01-10 2015-09 1661-6596 https://pubs.kist.re.kr/handle/201004/125047 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 -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. English Multidisciplinary Digital Publishing Institute (MDPI) Monitoring of Intracellular Tau Aggregation Regulated by OGA/OGT Inhibitors Article 10.3390/ijms160920212 1 International Journal of Molecular Sciences, v.16, no.9, pp.20212 - 20224 International Journal of Molecular Sciences 16 9 20212 20224 N scie scopus 000364541000008 2-s2.0-84940523812 Biochemistry & Molecular Biology Chemistry, Multidisciplinary Biochemistry & Molecular Biology Chemistry Article ALZHEIMERS-DISEASE O-GLCNACYLATION GLUCOSE-METABOLISM PROTEIN-TAU PHOSPHORYLATION BRAIN MICROTUBULES COMPLEX tau protein O-GlcNAcylation O-GlcNAc transferase O-GlcNAcase tau phosphorylation tau aggregation