Single-molecule imaging reveals that small amyloid-β1–42 oligomers interact with the cellular prion protein (PrPC)

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Ganzinger, Kristina A., Narayan, Priyanka, Qamar, Seema S., Weimann, Laura, Ranasinghe, Rohan T., Aguzzi, Adriano, Dobson, Christopher M., McColl, James, St George-Hyslop, Peter and Klenerman, David (2014) Single-molecule imaging reveals that small amyloid-β1–42 oligomers interact with the cellular prion protein (PrPC). ChemBioChem, 15 (17). pp. 2515-2521. ISSN 1439-4227

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Abstract

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 (PrPC) on live neuronal cells. Our results show that, at nanomolar concentrations, oAβ42 interacts with PrPC and that the species bound to PrPC 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.

Item Type:	Article
Additional Information:	Research Funding: Engineering and Physical Sciences Research Council (EPSRC); Studienstiftung des deutschen Volkes; Marshall Aid Commemoration Commission; National Science Foundation; Wellcome Trust; Augustus Newman Foundation
Faculty \ School:	Faculty of Science > School of Biological Sciences
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	15 Aug 2022 15:31
Last Modified:	22 Oct 2022 07:53
URI:	https://ueaeprints.uea.ac.uk/id/eprint/87270
DOI:	10.1002/cbic.201402377

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