Characterization of a single-chain variable fragment recognizing a linear epitope of aβ: a biotechnical tool for studies on Alzheimer's disease?

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with devastating effects. Currently, therapeutic options are limited to symptomatic treatment. For more than a decade, research focused on immunotherapy for the causal treatment of AD. However, clinical trials with active immu...

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Autores principales:	Silke Dornieden, Andreas Müller-Schiffmann, Heinrich Sticht, Nan Jiang, Yeliz Cinar, Michael Wördehoff, Carsten Korth, Susanne Aileen Funke, Dieter Willbold
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/121dd23d47ec4c12979a8398704700cf
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spelling	oai:doaj.org-article:121dd23d47ec4c12979a8398704700cf2021-11-18T07:51:55ZCharacterization of a single-chain variable fragment recognizing a linear epitope of aβ: a biotechnical tool for studies on Alzheimer's disease?1932-620310.1371/journal.pone.0059820https://doaj.org/article/121dd23d47ec4c12979a8398704700cf2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23555792/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Alzheimer's disease (AD) is a progressive neurodegenerative disorder with devastating effects. Currently, therapeutic options are limited to symptomatic treatment. For more than a decade, research focused on immunotherapy for the causal treatment of AD. However, clinical trials with active immunization using Aβ encountered severe complications, for example meningoencephalitis. Consequently, attention focused on passive immunization using antibodies. As an alternative to large immunoglobulins (IgGs), Aβ binding single-chain variable fragments (scFvs) were used for diagnostic and therapeutic research approaches. scFvs can be expressed in E. coli and may provide improved pharmacokinetic properties like increased blood-brain barrier permeability or reduced side-effects in vivo. In this study, we constructed an scFv from an Aβ binding IgG, designated IC16, which binds the N-terminal region of Aβ (Aβ(1-8)). scFv-IC16 was expressed in E. coli, purified and characterized with respect to its interaction with different Aβ species and its influence on Aβ fibril formation. We were able to show that scFv-IC16 strongly influenced the aggregation behavior of Aβ and could be applied as an Aβ detection probe for plaque staining in the brains of transgenic AD model mice. The results indicate potential for therapy and diagnosis of AD.Silke DorniedenAndreas Müller-SchiffmannHeinrich StichtNan JiangYeliz CinarMichael WördehoffCarsten KorthSusanne Aileen FunkeDieter WillboldPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e59820 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Silke Dornieden Andreas Müller-Schiffmann Heinrich Sticht Nan Jiang Yeliz Cinar Michael Wördehoff Carsten Korth Susanne Aileen Funke Dieter Willbold Characterization of a single-chain variable fragment recognizing a linear epitope of aβ: a biotechnical tool for studies on Alzheimer's disease?
description	Alzheimer's disease (AD) is a progressive neurodegenerative disorder with devastating effects. Currently, therapeutic options are limited to symptomatic treatment. For more than a decade, research focused on immunotherapy for the causal treatment of AD. However, clinical trials with active immunization using Aβ encountered severe complications, for example meningoencephalitis. Consequently, attention focused on passive immunization using antibodies. As an alternative to large immunoglobulins (IgGs), Aβ binding single-chain variable fragments (scFvs) were used for diagnostic and therapeutic research approaches. scFvs can be expressed in E. coli and may provide improved pharmacokinetic properties like increased blood-brain barrier permeability or reduced side-effects in vivo. In this study, we constructed an scFv from an Aβ binding IgG, designated IC16, which binds the N-terminal region of Aβ (Aβ(1-8)). scFv-IC16 was expressed in E. coli, purified and characterized with respect to its interaction with different Aβ species and its influence on Aβ fibril formation. We were able to show that scFv-IC16 strongly influenced the aggregation behavior of Aβ and could be applied as an Aβ detection probe for plaque staining in the brains of transgenic AD model mice. The results indicate potential for therapy and diagnosis of AD.
format	article
author	Silke Dornieden Andreas Müller-Schiffmann Heinrich Sticht Nan Jiang Yeliz Cinar Michael Wördehoff Carsten Korth Susanne Aileen Funke Dieter Willbold
author_facet	Silke Dornieden Andreas Müller-Schiffmann Heinrich Sticht Nan Jiang Yeliz Cinar Michael Wördehoff Carsten Korth Susanne Aileen Funke Dieter Willbold
author_sort	Silke Dornieden
title	Characterization of a single-chain variable fragment recognizing a linear epitope of aβ: a biotechnical tool for studies on Alzheimer's disease?
title_short	Characterization of a single-chain variable fragment recognizing a linear epitope of aβ: a biotechnical tool for studies on Alzheimer's disease?
title_full	Characterization of a single-chain variable fragment recognizing a linear epitope of aβ: a biotechnical tool for studies on Alzheimer's disease?
title_fullStr	Characterization of a single-chain variable fragment recognizing a linear epitope of aβ: a biotechnical tool for studies on Alzheimer's disease?
title_full_unstemmed	Characterization of a single-chain variable fragment recognizing a linear epitope of aβ: a biotechnical tool for studies on Alzheimer's disease?
title_sort	characterization of a single-chain variable fragment recognizing a linear epitope of aβ: a biotechnical tool for studies on alzheimer's disease?
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/121dd23d47ec4c12979a8398704700cf
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Characterization of a single-chain variable fragment recognizing a linear epitope of aβ: a biotechnical tool for studies on Alzheimer's disease?

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