[NMR paper] The cellular prion protein traps Alzheimer's A? in an oligomeric form and disassembles amyloid fibers.

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The cellular prion protein traps Alzheimer's A? in an oligomeric form and disassembles amyloid fibers.

Related Articles The cellular prion protein traps Alzheimer's A? in an oligomeric form and disassembles amyloid fibers.

FASEB J. 2013 Jan 30;

Authors: Younan ND, Sarell CJ, Davies P, Brown DR, Viles JH

Abstract
There is now strong evidence to show that the presence of the cellular prion protein (PrP(C)) mediates amyloid-? (A?) neurotoxicity in Alzheimer's disease (AD). Here, we probe the molecular details of the interaction between PrP(C) and A? and discover that substoichiometric amounts of PrP(C), as little as 1/20, relative to A? will strongly inhibit amyloid fibril formation. This effect is specific to the unstructured N-terminal domain of PrP(C). Electron microscopy indicates PrP(C) is able to trap A? in an oligomeric form. Unlike fibers, this oligomeric A? contains antiparallel ? sheet and binds to a oligomer specific conformational antibody. Our NMR studies show that a specific region of PrP(C), notably residues 95-113, binds to A? oligomers, but only once A? misfolds. The ability of PrP(C) to trap and concentrate A? in an oligomeric form and disassemble mature fibers suggests a mechanism by which PrP(C) might confer A? toxicity in AD, as oligomers are thought to be the toxic form of A?. Identification of a specific recognition site on PrP(C) that traps A? in an oligomeric form is potentially a therapeutic target for the treatment of Alzheimer's disease.-Younan, N. D., Sarell, C. J., Davies, P., Brown, D. R., Viles, J. H. The cellular prion protein traps Alzheimer's A? in an oligomeric form and disassembles amyloid fibers.


PMID: 23335053 [PubMed - as supplied by publisher]



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