Screening of tau protein kinase inhibitors in a tauopathy-relevant cell-based model of tau hyperphosphorylation and oligomerization.

PloS One
Hamad YadikarKevin K. Wang

Abstract

Tauopathies are a class of neurodegenerative disorders characterized by abnormal deposition of post-translationally modified tau protein in the human brain. Tauopathies are associated with Alzheimer's disease (AD), chronic traumatic encephalopathy (CTE), and other diseases. Hyperphosphorylation increases tau tendency to aggregate and form neurofibrillary tangles (NFT), a pathological hallmark of AD. In this study, okadaic acid (OA, 100 nM), a protein phosphatase 1/2A inhibitor, was treated for 24h in mouse neuroblastoma (N2a) and differentiated rat primary neuronal cortical cell cultures (CTX) to induce tau-hyperphosphorylation and oligomerization as a cell-based tauopathy model. Following the treatments, the effectiveness of different kinase inhibitors was assessed using the tauopathy-relevant tau antibodies through tau-immunoblotting, including the sites: pSer202/pThr205 (AT8), pThr181 (AT270), pSer202 (CP13), pSer396/pSer404 (PHF-1), and pThr231 (RZ3). OA-treated samples induced tau phosphorylation and oligomerization at all tested epitopes, forming a monomeric band (46-67 kDa) and oligomeric bands (170 kDa and 240 kDa). We found that TBB (a casein kinase II inhibitor), AR and LiCl (GSK-3 inhibitors), cyclosporin A (calcineu...Continue Reading

References

Jan 22, 1990·Brain Research·D S IimotoT Saitoh
Jun 1, 1989·Trends in Pharmacological Sciences·U T Rüegg, G M Burgess
Jan 30, 1987·Biochemical and Biophysical Research Communications·H KaseM Kaneko
Jan 1, 1970·Proceedings of the National Academy of Sciences of the United States of America·J B OlmstedJ Rosenbaum
Oct 28, 1998·Proceedings of the National Academy of Sciences of the United States of America·L N ClarkK C Wilhelmsen
Mar 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·N QinL Birnbaumer
May 11, 2000·Proceedings of the National Academy of Sciences of the United States of America·M von BergenE Mandelkow
Feb 13, 2001·Biochemical and Biophysical Research Communications·W J Ryves, A J Harwood
Feb 25, 2003·The British Journal of Ophthalmology·G ThuretP Gain
Apr 3, 2003·Journal of Endodontics·Juan J Segura-EgeaJuan R Calvo-Gutierrez
Jun 14, 2003·The Journal of Biological Chemistry·Victoria MakridesStuart C Feinstein
Aug 21, 2003·The Journal of Biological Chemistry·Ratan BhatJesús Avila
Jun 16, 2004·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Oliver DrognitzStefan Benz
Aug 19, 2004·The International Journal of Neuropsychopharmacology·Todd D GouldHusseini K Manji
Dec 24, 2004·Biochimica Et Biophysica Acta·William H Stoothoff, Gail V W Johnson
May 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Wendy NobleKaren Duff
Jun 14, 2006·Proceedings of the National Academy of Sciences of the United States of America·Sylvie Le CorreHanno M Roder
Dec 22, 2006·Journal of Medicinal Chemistry·Alexander J HenzingWilliam C Earnshaw
Jun 15, 2007·The European Journal of Neuroscience·Naruhiko SaharaAkihiko Takashima
Apr 24, 2008·Journal of Alzheimer's Disease : JAD·Gabriele HübingerHanno M Roder
Jun 6, 2008·Journal of Alzheimer's Disease : JAD·Marisol EspinozaPeter Davies
Apr 15, 2009·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·A C LudolphUNKNOWN Reisensburg Working Group for Tauopathies With Parkinsonism
Apr 28, 2009·Molecular Oncology·Tim P GreenGerard F Costello
May 5, 2009·Molecular Neurodegeneration·Kellen Voss, T Chris Gamblin
Feb 18, 2010·Neuro-degenerative Diseases·Branislav KovacechMichal Novak
Jul 29, 2010·The Journal of Biological Chemistry·Alejandra D AlonsoKhalid Iqbal
Sep 3, 2010·Brain Research·Zhang Zhang, James W Simpkins
Nov 5, 2010·Biochemistry·Cristian A Lasagna-ReevesRakez Kayed

❮ Previous
Next ❯

Citations

Dec 2, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Héctor Solís-ChagoyánGloria Benítez-King
Dec 11, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Rosa PurgatorioCosimo D Altomare
Dec 20, 2020·International Journal of Molecular Sciences·You Jung KangHansang Cho
Feb 12, 2021·Frontiers in Neurology·Karlen GazarianMar Pacheco-Herrero
May 15, 2021·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Neeraja Revi, Aravind Kumar Rengan
May 18, 2021·Signal Transduction and Targeted Therapy·Christian BorgoMaria Ruzzene
Aug 26, 2021·Molecular Neurobiology·Bianca GugliettiLyndsey E Collins-Praino
Aug 28, 2021·International Journal of Molecular Sciences·Stefania DemuroAndrea Cavalli
Oct 16, 2021·Der Nervenarzt·Gesine RespondekGünter U Höglinger

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic
electrophoresis

Software Mentioned

NIH ImageJ
GraphPad Prism

Related Concepts

Related Feeds

Brain Lower Grade Glioma

Low grade gliomas in the brain form from oligodendrocytes and astrocytes and are the slowest-growing glioma in adults. Discover the latest research on these brain tumors here.

Alzheimer's Disease: Tau & TDP-43

Alzheimer's disease is a neurodegenerative disease. This feed focuses on the underlying role of tau proteins and TAR DNA-binding protein 43, as well as other genetic factors, in Alzheimer's disease.