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Single-Molecule Imaging Reveals that Small Amyloid-β(1–42) Oligomers Interact with the Cellular Prion Protein (PrP(C))

Oligomers of the amyloid-β peptide (Aβ) play a central role in the pathogenesis of Alzheimer’s disease and have been suggested to induce neurotoxicity by binding to a plethora of cell-surface receptors. However, the heterogeneous mixtures of oligomers of varying sizes and conformations formed by Aβ4...

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Autores principales: Ganzinger, Kristina A, Narayan, Priyanka, Qamar, Seema S, Weimann, Laura, Ranasinghe, Rohan T, Aguzzi, Adriano, Dobson, Christopher M, McColl, James, St George-Hyslop, Peter, Klenerman, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: WILEY-VCH Verlag 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4371635/
https://www.ncbi.nlm.nih.gov/pubmed/25294384
http://dx.doi.org/10.1002/cbic.201402377
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author Ganzinger, Kristina A
Narayan, Priyanka
Qamar, Seema S
Weimann, Laura
Ranasinghe, Rohan T
Aguzzi, Adriano
Dobson, Christopher M
McColl, James
St George-Hyslop, Peter
Klenerman, David
author_facet Ganzinger, Kristina A
Narayan, Priyanka
Qamar, Seema S
Weimann, Laura
Ranasinghe, Rohan T
Aguzzi, Adriano
Dobson, Christopher M
McColl, James
St George-Hyslop, Peter
Klenerman, David
author_sort Ganzinger, Kristina A
collection PubMed
description Oligomers of the amyloid-β peptide (Aβ) play a central role in the pathogenesis of Alzheimer’s disease and have been suggested to induce neurotoxicity by binding to a plethora of cell-surface receptors. However, the heterogeneous mixtures of oligomers of varying sizes and conformations formed by Aβ42 have obscured the nature of the oligomeric species that bind to a given receptor. Here, we have used single-molecule imaging to characterize Aβ42 oligomers (oAβ42) and to confirm the controversial interaction of oAβ42 with the cellular prion protein (PrP(C)) on live neuronal cells. Our results show that, at nanomolar concentrations, oAβ42 interacts with PrP(C) and that the species bound to PrP(C) are predominantly small oligomers (dimers and trimers). Single-molecule biophysical studies can thus aid in deciphering the mechanisms that underlie receptor-mediated oAβ-induced neurotoxicity, and ultimately facilitate the discovery of novel inhibitors of these pathways.
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spelling pubmed-43716352015-03-26 Single-Molecule Imaging Reveals that Small Amyloid-β(1–42) Oligomers Interact with the Cellular Prion Protein (PrP(C)) Ganzinger, Kristina A Narayan, Priyanka Qamar, Seema S Weimann, Laura Ranasinghe, Rohan T Aguzzi, Adriano Dobson, Christopher M McColl, James St George-Hyslop, Peter Klenerman, David Chembiochem Communications Oligomers of the amyloid-β peptide (Aβ) play a central role in the pathogenesis of Alzheimer’s disease and have been suggested to induce neurotoxicity by binding to a plethora of cell-surface receptors. However, the heterogeneous mixtures of oligomers of varying sizes and conformations formed by Aβ42 have obscured the nature of the oligomeric species that bind to a given receptor. Here, we have used single-molecule imaging to characterize Aβ42 oligomers (oAβ42) and to confirm the controversial interaction of oAβ42 with the cellular prion protein (PrP(C)) on live neuronal cells. Our results show that, at nanomolar concentrations, oAβ42 interacts with PrP(C) and that the species bound to PrP(C) are predominantly small oligomers (dimers and trimers). Single-molecule biophysical studies can thus aid in deciphering the mechanisms that underlie receptor-mediated oAβ-induced neurotoxicity, and ultimately facilitate the discovery of novel inhibitors of these pathways. WILEY-VCH Verlag 2014-11-24 2014-10-07 /pmc/articles/PMC4371635/ /pubmed/25294384 http://dx.doi.org/10.1002/cbic.201402377 Text en © 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Communications
Ganzinger, Kristina A
Narayan, Priyanka
Qamar, Seema S
Weimann, Laura
Ranasinghe, Rohan T
Aguzzi, Adriano
Dobson, Christopher M
McColl, James
St George-Hyslop, Peter
Klenerman, David
Single-Molecule Imaging Reveals that Small Amyloid-β(1–42) Oligomers Interact with the Cellular Prion Protein (PrP(C))
title Single-Molecule Imaging Reveals that Small Amyloid-β(1–42) Oligomers Interact with the Cellular Prion Protein (PrP(C))
title_full Single-Molecule Imaging Reveals that Small Amyloid-β(1–42) Oligomers Interact with the Cellular Prion Protein (PrP(C))
title_fullStr Single-Molecule Imaging Reveals that Small Amyloid-β(1–42) Oligomers Interact with the Cellular Prion Protein (PrP(C))
title_full_unstemmed Single-Molecule Imaging Reveals that Small Amyloid-β(1–42) Oligomers Interact with the Cellular Prion Protein (PrP(C))
title_short Single-Molecule Imaging Reveals that Small Amyloid-β(1–42) Oligomers Interact with the Cellular Prion Protein (PrP(C))
title_sort single-molecule imaging reveals that small amyloid-β(1–42) oligomers interact with the cellular prion protein (prp(c))
topic Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4371635/
https://www.ncbi.nlm.nih.gov/pubmed/25294384
http://dx.doi.org/10.1002/cbic.201402377
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