Details

Autor(en) / Beteiligte

• 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

Titel

Single-Molecule Imaging Reveals that Small Amyloid-β1-42 Oligomers Interact with the Cellular Prion Protein (PrPC)

Ist Teil von

• Chembiochem : a European journal of chemical biology, 2014-11, Vol.15 (17), p.2515-2521

Ort / Verlag

Weinheim: WILEY-VCH Verlag

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. Small oligomers bind PrPC: TIRF microscopy and a single‐particle tracking approach have determined that amyloid‐β peptide oligomers (oAβ) interact with the cellular prion protein (PrPC) on live neuronal cells. Having dissected this interaction at the single‐molecule level, we estimate that predominantly small oAβ42 species (dimers and trimers) bind to PrPC.