Stable mutated tau441 transfected SH-SY5Y cells as screening tool for Alzheimer's disease drug candidates.

Journal of Molecular Neuroscience : MN
Tina LöfflerBirgit Hutter-Paier

Abstract

The role of hyperphosphorylation of the microtubule-associated protein tau in the pathological processes of several neurodegenerative diseases is becoming better understood. Consequently, development of new compounds capable of preventing tau hyperphosphorylation is an increasingly hot topic. For this reason, dependable in vitro and in vivo models that reflect tau hyperphosphorylation in human diseases are needed. In this study, we generated and validated an in vitro model appropriate to test potential curative and preventive compound effects on tau phosphorylation. For this purpose, a stably transfected SH-SY5Y cell line was constructed over-expressing mutant human tau441 (SH-SY5Y-TMHT441). Analyses of expression levels and tau phosphorylation status in untreated cells confirmed relevance to human diseases. Subsequently, the effect of different established kinase inhibitors on tau phosphorylation (e.g., residues Thr231, Thr181, and Ser396) was examined. It was shown with several methods including immunosorbent assays and mass spectrometry that the phosphorylation pattern of tau in SH-SY5Y-TMHT441 cells can be reliably modulated by these compounds, specifically targeting JNK, GSK-3, CDK1/5, and CK1. These four protein kinases a...Continue Reading

References

Dec 1, 1995·Molecular Biology of the Cell·B TrinczekE Mandelkow
Jan 17, 1996·Annals of the New York Academy of Sciences·M Goedert
Sep 28, 1999·Journal of Neuropathology and Experimental Neurology·J J PeiR F Cowburn
Oct 9, 1999·The American Journal of Pathology·N GhoshalJ Kuret
Apr 6, 2000·The Journal of Biological Chemistry·N MashhoonJ Kuret
May 18, 2000·Brain Research·K YasojimaP L McGeer
Nov 22, 2001·Proceedings of the National Academy of Sciences of the United States of America·B L BennettD W Anderson
Jul 19, 2002·Journal of Neuroscience Research·Terrence TownMike Mullan
Nov 26, 2002·Journal of Alzheimer's Disease : JAD·Carola OtthRicardo B Maccioni
Feb 13, 2003·Neuropathology and Applied Neurobiology·I FerrerE Tolosa
Feb 6, 2004·The Journal of Biological Chemistry·Guibin LiJeff Kuret
Nov 5, 2004·Science in China. Series C, Life Sciences·Xiaomei LiaoJianzhi Wang
Feb 16, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yoshitaka TatebayashiAkihiko Takashima
May 12, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Tobias EngelJosé J Lucas
Dec 16, 2006·Current Alzheimer Research·Mathew Blurton-Jones, Frank M Laferla
Feb 20, 2007·Biochimica Et Biophysica Acta·Gary L Johnson, Kazuhiro Nakamura
Jun 2, 2007·Nature Reviews. Drug Discovery·Michael P Mazanetz, Peter M Fischer
Jun 15, 2007·The Journal of Biological Chemistry·Diane P HangerBrian H Anderton
Dec 15, 2007·The American Journal of Pathology·Patrice DelobelMichel Goedert
May 2, 2008·Progress in Neurobiology·Jian-Zhi Wang, Fei Liu
Oct 16, 2008·Molecular Systems Biology·Vinzenz LangeRuedi Aebersold
Feb 28, 2009·Trends in Molecular Medicine·Diane P HangerWendy Noble
Mar 20, 2010·Biochemical Society Transactions·Catherine M CowanAmritpal Mudher
Apr 2, 2010·Nature·Alix de CalignonBradley T Hyman

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Citations

Mar 1, 2015·Neuropharmacology·Marta LeirósLuis M Botana
Feb 7, 2016·Journal of Neuropathology and Experimental Neurology·Misol AhnStephen J DeArmond
Jan 27, 2015·Neurobiology of Aging·Huilai TianMichael R Sierks
Sep 28, 2016·Neurobiology of Aging·Elyse RosaMargaret Fahnestock
Apr 29, 2014·World Journal of Stem Cells·Lisa MohametChristopher M Ward

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Methods Mentioned

BETA
transgenic
Transfection
Protein Assay
Assay

Clinical Trials Mentioned

NCT01056965
NCT01049399
NCT01350363

Software Mentioned

Graph Pad Prism4
Mesoscale Discovery

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