Two-dimensional electrophoresis of tau mutants reveals specific phosphorylation pattern likely linked to early tau conformational changes.

The role of Tau phosphorylation in neurofibrillary degeneration linked to Alzheimer's disease remains to be established. While transgenic mice based on FTDP-17 Tau mutations recapitulate hallmarks of neurofibrillary degeneration, cell models could be helpful for exploratory studies on molecular...

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Autores principales:	Alexis Bretteville, Kunie Ando, Antoine Ghestem, Anne Loyens, Séverine Bégard, Jean-Claude Beauvillain, Nicolas Sergeant, Malika Hamdane, Luc Buée
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/be175fede5414d1c891f064a9fc359ad
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spelling	oai:doaj.org-article:be175fede5414d1c891f064a9fc359ad2021-11-25T06:16:40ZTwo-dimensional electrophoresis of tau mutants reveals specific phosphorylation pattern likely linked to early tau conformational changes.1932-620310.1371/journal.pone.0004843https://doaj.org/article/be175fede5414d1c891f064a9fc359ad2009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19290042/?tool=EBIhttps://doaj.org/toc/1932-6203The role of Tau phosphorylation in neurofibrillary degeneration linked to Alzheimer's disease remains to be established. While transgenic mice based on FTDP-17 Tau mutations recapitulate hallmarks of neurofibrillary degeneration, cell models could be helpful for exploratory studies on molecular mechanisms underlying Tau pathology. Here, "human neuronal cell lines" overexpressing Wild Type or mutated Tau were established. Two-dimensional electrophoresis highlights that mutated Tau displayed a specific phosphorylation pattern, which occurs in parallel to the formation of Tau clusters as visualized by electron microscopy. In fact, this pattern is also displayed before Tau pathology onset in a well established mouse model relevant to Tau aggregation in Alzheimer's disease. This study suggests first that pathological Tau mutations may change the distribution of phosphate groups. Secondly, it is possible that this molecular event could be one of the first Tau modifications in the neurofibrillary degenerative process, as this phenomenon appears prior to Tau pathology in an in vivo model and is linked to early steps of Tau nucleation in Tau mutants cell lines. Such cell lines consist in suitable and evolving models to investigate additional factors involved in molecular pathways leading to whole Tau aggregation.Alexis BrettevilleKunie AndoAntoine GhestemAnne LoyensSéverine BégardJean-Claude BeauvillainNicolas SergeantMalika HamdaneLuc BuéePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 3, p e4843 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alexis Bretteville Kunie Ando Antoine Ghestem Anne Loyens Séverine Bégard Jean-Claude Beauvillain Nicolas Sergeant Malika Hamdane Luc Buée Two-dimensional electrophoresis of tau mutants reveals specific phosphorylation pattern likely linked to early tau conformational changes.
description	The role of Tau phosphorylation in neurofibrillary degeneration linked to Alzheimer's disease remains to be established. While transgenic mice based on FTDP-17 Tau mutations recapitulate hallmarks of neurofibrillary degeneration, cell models could be helpful for exploratory studies on molecular mechanisms underlying Tau pathology. Here, "human neuronal cell lines" overexpressing Wild Type or mutated Tau were established. Two-dimensional electrophoresis highlights that mutated Tau displayed a specific phosphorylation pattern, which occurs in parallel to the formation of Tau clusters as visualized by electron microscopy. In fact, this pattern is also displayed before Tau pathology onset in a well established mouse model relevant to Tau aggregation in Alzheimer's disease. This study suggests first that pathological Tau mutations may change the distribution of phosphate groups. Secondly, it is possible that this molecular event could be one of the first Tau modifications in the neurofibrillary degenerative process, as this phenomenon appears prior to Tau pathology in an in vivo model and is linked to early steps of Tau nucleation in Tau mutants cell lines. Such cell lines consist in suitable and evolving models to investigate additional factors involved in molecular pathways leading to whole Tau aggregation.
format	article
author	Alexis Bretteville Kunie Ando Antoine Ghestem Anne Loyens Séverine Bégard Jean-Claude Beauvillain Nicolas Sergeant Malika Hamdane Luc Buée
author_facet	Alexis Bretteville Kunie Ando Antoine Ghestem Anne Loyens Séverine Bégard Jean-Claude Beauvillain Nicolas Sergeant Malika Hamdane Luc Buée
author_sort	Alexis Bretteville
title	Two-dimensional electrophoresis of tau mutants reveals specific phosphorylation pattern likely linked to early tau conformational changes.
title_short	Two-dimensional electrophoresis of tau mutants reveals specific phosphorylation pattern likely linked to early tau conformational changes.
title_full	Two-dimensional electrophoresis of tau mutants reveals specific phosphorylation pattern likely linked to early tau conformational changes.
title_fullStr	Two-dimensional electrophoresis of tau mutants reveals specific phosphorylation pattern likely linked to early tau conformational changes.
title_full_unstemmed	Two-dimensional electrophoresis of tau mutants reveals specific phosphorylation pattern likely linked to early tau conformational changes.
title_sort	two-dimensional electrophoresis of tau mutants reveals specific phosphorylation pattern likely linked to early tau conformational changes.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/be175fede5414d1c891f064a9fc359ad
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Two-dimensional electrophoresis of tau mutants reveals specific phosphorylation pattern likely linked to early tau conformational changes.

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