Central amyloid-beta-specific single chain variable fragment ameliorates A-beta aggregation and neurotoxicity

Nisbet, R. M., Nigro, J., Breheney, K., Caine, J., Hattarki, M. K. and Nuttall, S. D. (2013) Central amyloid-beta-specific single chain variable fragment ameliorates A-beta aggregation and neurotoxicity. Protein Engineering Design and Selection, 26 10: 571-580. doi:10.1093/protein/gzt025


Author Nisbet, R. M.
Nigro, J.
Breheney, K.
Caine, J.
Hattarki, M. K.
Nuttall, S. D.
Title Central amyloid-beta-specific single chain variable fragment ameliorates A-beta aggregation and neurotoxicity
Formatted title
Central amyloid-β-specific single chain variable fragment ameliorates Aβ aggregation and neurotoxicity
Journal name Protein Engineering Design and Selection   Check publisher's open access policy
ISSN 1741-0126
1741-0134
Publication date 2013-10-01
Year available 2013
Sub-type Article (original research)
DOI 10.1093/protein/gzt025
Open Access Status Not Open Access
Volume 26
Issue 10
Start page 571
End page 580
Total pages 10
Editor Regina Murphy
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Formatted abstract
Anti-amyloid-β immunotherapies are a promising therapeutic approach for the treatment and prevention of Alzheimer's disease (AD). Single chain antibody fragments (scFv) are an attractive alternative to whole antibodies due to their small size, single polypeptide format and inability to stimulate potentially undesirable Fc-mediated immune effector functions. We have generated the scFv derivative of anti-Aβ monoclonal antibody, 1E8, known to target residues 17–22 of Aβ. Here we show that the soluble 1E8 scFv binds to the central region of Aβ with an affinity of ~55 nM and significantly reduces fibril formation of Aβ1–42. Furthermore, 1E8 scFv ameliorates Aβ1–42-mediated toxicity in the PC12 cell line and murine primary neuronal cultures. This ability to both target the central region of Aβ and prevent Aβ1–42 neurotoxicity in vitro makes it a promising therapeutic antibody building block for further functionalization, toward the treatment of AD.
Keyword Alzheimer’s disease
Amyloid-beta
Immunotherapy
Single chain antibody
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
Queensland Brain Institute Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 10 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 10 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Thu, 06 Mar 2014, 23:51:28 EST by Rebecca Nisbet on behalf of Clem Jones Centre for Ageing Dementia Research