Amyloid-β nanotubes are associated with prion protein-dependent synaptotoxicity
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Author
Nicoll, Andrew J.
Panico, Silvia
Freir, Darragh B.
Wright, Daniel
Terry, Cassandra
Risse, Emmanuel
Herron, Caroline E.
O’Malley, Tiernan
Wadsworth, Jonathan D. F.
Farrow, Mark A.
Saibil, Helen R.
Collinge, John
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/ncomms3416Metadata
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Nicoll, A. J., S. Panico, D. B. Freir, D. Wright, C. Terry, E. Risse, C. E. Herron, et al. 2013. “Amyloid-β nanotubes are associated with prion protein-dependent synaptotoxicity.” Nature Communications 4 (1): 2416. doi:10.1038/ncomms3416. http://dx.doi.org/10.1038/ncomms3416.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 Aβ1–42. 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 Aβ1–42 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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3908552/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879913
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