Monitoring of Intracellular Tau Aggregation Regulated by OGA/OGT Inhibitors

International Journal of Molecular Sciences
Sungsu LimYun Kyung Kim

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.

References

Oct 1, 1992·Molecular Biology of the Cell·D N DrechselM W Kirschner
Nov 15, 1996·The Journal of Biological Chemistry·C S ArnoldG W Hart
Jul 13, 2004·The Journal of Biological Chemistry·Lance WellsGerald W Hart
Jul 14, 2004·Proceedings of the National Academy of Sciences of the United States of America·Fei LiuCheng-Xin Gong
Sep 18, 2004·The Journal of Biological Chemistry·Shi Jie LiuJian Zhi Wang
Apr 28, 2005·The Journal of Biological Chemistry·Marco D MukraschMarkus Zweckstetter
Feb 28, 2006·Biophysical Journal·Itsushi Minoura, Etsuko Muto
Jun 2, 2007·Nature Reviews. Drug Discovery·Michael P Mazanetz, Peter M Fischer
Jul 1, 2008·Nature Chemical Biology·Scott A YuzwaDavid J Vocadlo
Nov 16, 2011·Nature Chemical Biology·Jiaoyang JiangSuzanne Walker
Mar 1, 2012·Nature Chemical Biology·Scott A YuzwaDavid J Vocadlo
Dec 6, 2014·Nature Communications·Dong Hoon HanMin Jae Lee

❮ Previous
Next ❯

Citations

Feb 27, 2017·Cellular and Molecular Neurobiology·Rongrong ChenXiaojuan Liu
Apr 7, 2018·Experimental & Molecular Medicine·Sungsu LimYun Kyung Kim
Oct 3, 2018·International Journal of Molecular Sciences·Seulgi ShinYun Kyung Kim
Feb 3, 2018·Journal of Enzyme Inhibition and Medicinal Chemistry·Shengqiang ShenJianjun Zhang
May 16, 2019·Journal of Zhejiang University. Science. B·Hao Nie, Wen Yi
May 2, 2018·Current Medicinal Chemistry·Chit TamTao Zuo
Jul 11, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Qi ChengChen-Jie Fang
Jan 3, 2020·Neuromolecular Medicine·Jinsu ParkDong-Gyu Jo
Sep 5, 2019·International Journal of Molecular Sciences·Hyeanjeong JeongYun Kyung Kim
Oct 23, 2020·International Journal of Molecular Sciences·Vidyasagar Naik BukkeTommaso Cassano
Nov 17, 2020·Frontiers in Oncology·Donglu WuHaoming Luo
Nov 17, 2020·Journal of Medicinal Chemistry·Carlos M Martínez-ViturroJosé M Bartolomé-Nebreda
Jul 24, 2021·The Biochemical Journal·Aaron T Balana, Matthew R Pratt
Apr 16, 2019·ACS Chemical Neuroscience·Philip RyanSantosh Rudrawar

❮ Previous
Next ❯

Methods Mentioned

BETA
Fluorescence
Assay
chemical treatment

Software Mentioned

Harmony
Operetta
Operetta ® High Contents Image System
ImageJ

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.