Amyloid-b nanotubes are associated with prion protein-dependent synaptotoxicity
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|Title:||Amyloid-b nanotubes are associated with prion protein-dependent synaptotoxicity||Authors:||Nicoll, Andrew J.
|Permanent link:||http://hdl.handle.net/10197/6816||Date:||11-Sep-2013||Abstract:||Growing evidence suggests water-soluble, non-fibrillar forms of amyloid-β protein (Aβ) have important roles in Alzheimer's disease with toxicities mimicked by synthetic Aβ(1-42). However, no defined toxic structures acting via specific receptors have been identified and roles of proposed receptors, such as prion protein (PrP), remain controversial. Here we quantify binding to PrP of Aβ(1-42) after different durations of aggregation. We show PrP-binding and PrP-dependent inhibition of long-term potentiation (LTP) correlate with the presence of protofibrils. Globular oligomers bind less avidly to PrP and do not inhibit LTP, whereas fibrils inhibit LTP in a PrP-independent manner. That only certain transient Aβ assemblies cause PrP-dependent toxicity explains conflicting reports regarding the involvement of PrP in Aβ-induced impairments. We show that these protofibrils contain a defined nanotubular structure with a previously unidentified triple helical conformation. Blocking the formation of Aβ nanotubes or their interaction with PrP might have a role in treatment of Alzheimer's disease.||Type of material:||Journal Article||Publisher:||Nature Publishing Group||Copyright (published version):||2013 Macmillan Publishers Limited||Keywords:||Alzheimer's disease;Aβ nanotubes||DOI:||10.1038/ncomms3416||Language:||en||Status of Item:||Peer reviewed|
|Appears in Collections:||Biomolecular and Biomedical Science Research Collection|
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