Imperial College London
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Dr Francesco A. Aprile

Faculty of Natural Sciences, Department of Chemistry

Lecturer in Chemistry
 
 
 
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Contact

 

+44 (0)20 7594 5545f.aprile Website

 
 
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Location

 

110FMolecular Sciences Research HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Aprile:2020:10.1073/pnas.1919464117,
author = {Aprile, FA and Sormanni, P and Podpolny, M and Chhangur, S and Needham, L-M and Ruggeri, FS and Perni, M and Limbocker, R and Heller, GT and Sneideris, T and Scheidt, T and Mannini, B and Habchi, J and Lee, SF and Salinas, PC and Knowles, TPJ and Dobson, CM and Vendruscolo, M},
doi = {10.1073/pnas.1919464117},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
pages = {13509--13518},
title = {Rational design of a conformation-specific antibody for the quantification of A beta oligomers},
url = {http://dx.doi.org/10.1073/pnas.1919464117},
volume = {117},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Protein misfolding and aggregation is the hallmark of numerous human disorders, including Alzheimer’s disease. This process involves the formation of transient and heterogeneous soluble oligomers, some of which are highly cytotoxic. A major challenge for the development of effective diagnostic and therapeutic tools is thus the detection and quantification of these elusive oligomers. Here, to address this problem, we develop a two-step rational design method for the discovery of oligomer-specific antibodies. The first step consists of an “antigen scanning” phase in which an initial panel of antibodies is designed to bind different epitopes covering the entire sequence of a target protein. This procedure enables the determination through in vitro assays of the regions exposed in the oligomers but not in the fibrillar deposits. The second step involves an “epitope mining” phase, in which a second panel of antibodies is designed to specifically target the regions identified during the scanning step. We illustrate this method in the case of the amyloid β (Aβ) peptide, whose oligomers are associated with Alzheimer’s disease. Our results show that this approach enables the accurate detection and quantification of Aβ oligomers in vitro, and in Caenorhabditis elegans and mouse hippocampal tissues.
AU  - Aprile,FA
AU  - Sormanni,P
AU  - Podpolny,M
AU  - Chhangur,S
AU  - Needham,L-M
AU  - Ruggeri,FS
AU  - Perni,M
AU  - Limbocker,R
AU  - Heller,GT
AU  - Sneideris,T
AU  - Scheidt,T
AU  - Mannini,B
AU  - Habchi,J
AU  - Lee,SF
AU  - Salinas,PC
AU  - Knowles,TPJ
AU  - Dobson,CM
AU  - Vendruscolo,M
DO  - 10.1073/pnas.1919464117
EP  - 13518
PY  - 2020///
SN  - 0027-8424
SP  - 13509
TI  - Rational design of a conformation-specific antibody for the quantification of A beta oligomers
T2  - Proceedings of the National Academy of Sciences of the United States of America
UR  - http://dx.doi.org/10.1073/pnas.1919464117
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000548656500015&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.pnas.org/content/117/24/13509
UR  - http://hdl.handle.net/10044/1/84526
VL  - 117
ER  -
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