Biophysical properties of a tau seed

Abstract Pathogenesis of tauopathies involves conversion of tau monomer into pathological tau conformers that serve as templates to recruit native tau into growing assemblies. Small soluble tau seeds have been proposed to drive pathological tau assembly in vitro, in cells and in vivo. We have previo...

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Autores principales:	Zhiqiang Hou, Dailu Chen, Bryan D. Ryder, Lukasz A. Joachimiak
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3a52c751ad3f486f923d73a2de32d49c
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spelling	oai:doaj.org-article:3a52c751ad3f486f923d73a2de32d49c2021-12-02T18:18:33ZBiophysical properties of a tau seed10.1038/s41598-021-93093-z2045-2322https://doaj.org/article/3a52c751ad3f486f923d73a2de32d49c2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93093-zhttps://doaj.org/toc/2045-2322Abstract Pathogenesis of tauopathies involves conversion of tau monomer into pathological tau conformers that serve as templates to recruit native tau into growing assemblies. Small soluble tau seeds have been proposed to drive pathological tau assembly in vitro, in cells and in vivo. We have previously described the isolation of monomeric pathogenic tau seeds derived from recombinant samples and tauopathy tissues but in-depth biophysical characterization of these species has not been done. Here we describe a chromatographic method to isolate recombinant soluble tau seeds derived from heparin treatment. We used biochemical and biophysical approaches to show that the seeds are predominantly monomeric and have the capacity to nucleate aggregation of inert forms of tau in vitro and in cells. Finally, we used crosslinking mass spectrometry to identify the topological changes in tau as it converts from an inert state to a pathogenic seed. Future studies will reveal the relationship between soluble seeds and structural polymorphs derived from tauopathies to help diagnose and develop therapeutics targeting specific tauopathies.Zhiqiang HouDailu ChenBryan D. RyderLukasz A. JoachimiakNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zhiqiang Hou Dailu Chen Bryan D. Ryder Lukasz A. Joachimiak Biophysical properties of a tau seed
description	Abstract Pathogenesis of tauopathies involves conversion of tau monomer into pathological tau conformers that serve as templates to recruit native tau into growing assemblies. Small soluble tau seeds have been proposed to drive pathological tau assembly in vitro, in cells and in vivo. We have previously described the isolation of monomeric pathogenic tau seeds derived from recombinant samples and tauopathy tissues but in-depth biophysical characterization of these species has not been done. Here we describe a chromatographic method to isolate recombinant soluble tau seeds derived from heparin treatment. We used biochemical and biophysical approaches to show that the seeds are predominantly monomeric and have the capacity to nucleate aggregation of inert forms of tau in vitro and in cells. Finally, we used crosslinking mass spectrometry to identify the topological changes in tau as it converts from an inert state to a pathogenic seed. Future studies will reveal the relationship between soluble seeds and structural polymorphs derived from tauopathies to help diagnose and develop therapeutics targeting specific tauopathies.
format	article
author	Zhiqiang Hou Dailu Chen Bryan D. Ryder Lukasz A. Joachimiak
author_facet	Zhiqiang Hou Dailu Chen Bryan D. Ryder Lukasz A. Joachimiak
author_sort	Zhiqiang Hou
title	Biophysical properties of a tau seed
title_short	Biophysical properties of a tau seed
title_full	Biophysical properties of a tau seed
title_fullStr	Biophysical properties of a tau seed
title_full_unstemmed	Biophysical properties of a tau seed
title_sort	biophysical properties of a tau seed
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3a52c751ad3f486f923d73a2de32d49c
work_keys_str_mv	AT zhiqianghou biophysicalpropertiesofatauseed AT dailuchen biophysicalpropertiesofatauseed AT bryandryder biophysicalpropertiesofatauseed AT lukaszajoachimiak biophysicalpropertiesofatauseed
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Biophysical properties of a tau seed

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