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Int. J. Mol. Sci. 2015, 16(9), 20212-20224; doi:10.3390/ijms160920212

Monitoring of Intracellular Tau Aggregation Regulated by OGA/OGT Inhibitors

1
Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 136-791, South Korea
2
Biological Chemistry, University of Science and Technology (UST), Daejeon 305-333, South Korea
3
Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 136-791, South Korea
4
Department of Neuroscience, University of Science and Technology (UST), Daejeon 305-333, South Korea
*
Authors to whom correspondence should be addressed.
Academic Editor: Salvador Ventura
Received: 19 June 2015 / Revised: 12 August 2015 / Accepted: 18 August 2015 / Published: 26 August 2015
(This article belongs to the Collection Protein Folding)
View Full-Text   |   Download PDF [3830 KB, uploaded 26 August 2015]   |  

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. View Full-Text
Keywords: tau protein; O-GlcNAcylation; O-GlcNAc transferase; O-GlcNAcase; tau phosphorylation; tau aggregation tau protein; O-GlcNAcylation; O-GlcNAc transferase; O-GlcNAcase; tau phosphorylation; tau aggregation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Lim, S.; Haque, M.M.; Nam, G.; Ryoo, N.; Rhim, H.; Kim, Y.K. Monitoring of Intracellular Tau Aggregation Regulated by OGA/OGT Inhibitors. Int. J. Mol. Sci. 2015, 16, 20212-20224.

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