The novel histone de acetylase 6 inhibitor, MPT0G211, ameliorates tau phosphorylation and cognitive deficits in an Alzheimer's disease model

Cell Death & Disease
Sheng-Jun FanChia-Ron Yang

Abstract

Alzheimer's disease (AD) is a dreadful neurodegenerative disease that leads to severe impairment of cognitive function, leading to a drastic decline in the quality of life. The primary pathological features of AD include senile plaques (SPs) and intracellular neurofibrillary tangles (NFTs), comprising aggregated amyloid β (Aβ) and hyperphosphorylated tau protein, respectively, in the hippocampus of AD patients. Histone deacetylase 6 (HDAC6) is a key enzyme in this neurodegenerative disease, in particular, as it relates to tau hyperphosphorylation. This study aimed to investigate the protective effects and mechanism of the novel HDAC6 inhibitor, MPT0G211, using an AD model. Our results indicated that MPT0G211 significantly reduced tau phosphorylation and aggregation, the processes highly correlated with the formation of NFTs. This HDAC6 inhibitory activity resulted in an increase in acetylated Hsp90, which decreased Hsp90 and HDAC6 binding, causing ubiquitination of phosphorylated tau proteins. In addition, a significant increase of phospho-glycogen synthase kinase-3β (phospho-GSK3β) on Ser9 (the inactive form) through Akt phosphorylation was associated with the inhibition of phospho-tau Ser396 in response to MPT0G211 treatment....Continue Reading

References

Mar 3, 1995·The Journal of Biological Chemistry·J Z WangK Iqbal
Aug 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·A TakashimaK Imahori
Jan 11, 2003·Proceedings of the National Academy of Sciences of the United States of America·Fei DouHuaxi Xu
Apr 30, 2003·Journal of Alzheimer's Disease : JAD·Ming-Sum Lee, Li-Huei Tsai
Jun 11, 2004·The Journal of Biological Chemistry·Alejandra del C AlonsoKhalid Iqbal
Dec 24, 2004·Biochimica Et Biophysica Acta·Roland BrandtNeelam Shahani
Jan 16, 2007·Molecular Cell·Bradley T ScrogginsLen Neckers
Feb 17, 2007·The Journal of Clinical Investigation·Chad A DickeyLeonard Petrucelli
Dec 28, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Tracy L Young-PearseDennis J Selkoe
Jan 9, 2008·Molecular and Cellular Biology·Yu ZhangPatrick Matthias
May 13, 2008·Trends in Cell Biology·Agustín Valenzuela-FernándezFrancisco Sánchez-Madrid
Jul 19, 2008·Journal of Neurochemistry·Huiping DingGail V W Johnson
Sep 29, 2009·Experimental Neurology·Félix HernándezJesús Avila
Jul 27, 2010·Progress in Neuro-psychopharmacology & Biological Psychiatry·Alexander Kurz, Robert Perneczky
Apr 12, 2012·Human Molecular Genetics·Casey CookLeonard Petrucelli
Nov 20, 2012·Biochemical and Biophysical Research Communications·Saori OdagiriKoichi Wakabayashi
Nov 28, 2012·EMBO Molecular Medicine·Nambirajan GovindarajanAndré Fischer
Jul 31, 2013·Neuropharmacology·R AnandAbbas Ali Mahdi
Jan 7, 2015·Molecular Neurobiology·Yanuar Alan Sulistio, Klaus Heese
Feb 26, 2015·Pharmacological Reports : PR·Anil Kumar Ekavali

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Citations

Apr 3, 2019·International Journal of Molecular Sciences·Jonathan IaconelliRakesh Karmacharya
Dec 24, 2019·Expert Opinion on Therapeutic Patents·Sida Shen, Alan P Kozikowski
Feb 6, 2020·Cancers·Hélène LossonMarc Diederich
Jun 13, 2020·The Journal of Biological Chemistry·Sarah J BackeMehdi Mollapour
Jul 9, 2020·European Journal of Nuclear Medicine and Molecular Imaging·Michel KooleTonya M Gilbert
Sep 5, 2019·International Journal of Molecular Sciences·Hyeanjeong JeongYun Kyung Kim
Feb 6, 2020·Cells·Sandeep MalampatiAnd Min Li
Nov 11, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Sravani PulyaBalaram Ghosh
Dec 31, 2020·Cells·Patrizia LoPresti
Apr 13, 2021·Expert Opinion on Therapeutic Targets·Fabio Coppedè
May 29, 2021·RSC Medicinal Chemistry·Alexandria M Chan, Steven Fletcher
Jul 22, 2018·Journal of Medicinal Chemistry·Hsueh-Yun LeeJing-Ping Liou
Jul 22, 2021·ChemMedChem·Xi Khai Wong, Keng Yoon Yeong
Jul 11, 2019·Journal of Natural Products·Jou-Man HuangChia-Ron Yang
Dec 16, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Kuan-Chung ChengHsueh-Cheng Chiang

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Methods Mentioned

BETA
acetylation
ubiquitination
transfections
fluorescence microscopy
flow cytometry
coimmunoprecipitation
transgenic
protein folding
transfection
immunoprecipitation

Software Mentioned

Cell Quest

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