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dc.contributor.authorLi, Huiyuan
dc.contributor.authorMonien, Bernhard H.
dc.contributor.authorLomakin, Aleksey
dc.contributor.authorZemel, Reeve
dc.contributor.authorFradinger, Erica A.
dc.contributor.authorTan, Miao
dc.contributor.authorSpring, Sean M.
dc.contributor.authorUrbanc, Brigita
dc.contributor.authorXie, Cui-Wei
dc.contributor.authorBenedek, George B.
dc.contributor.authorBitan, Gal
dc.date.accessioned2013-01-08T15:15:13Z
dc.date.available2013-01-08T15:15:13Z
dc.date.issued2010-08
dc.date.submitted2010-06
dc.identifier.issn0006-2960
dc.identifier.issn1520-4995
dc.identifier.urihttp://hdl.handle.net/1721.1/76186
dc.description.abstractOligomeric forms of amyloid β-protein (Aβ) are key neurotoxins in Alzheimer’s disease (AD). Previously, we found that C-terminal fragments (CTFs) of Aβ42 interfered with assembly of full-length Aβ42 and inhibited Aβ42-induced toxicity. To decipher the mechanism(s) by which CTFs affect Aβ42 assembly and neurotoxicity, here, we investigated the interaction between Aβ42 and CTFs using photoinduced cross-linking and dynamic light scattering. The results demonstrate that distinct parameters control CTF inhibition of Aβ42 assembly and Aβ42-induced toxicity. Inhibition of Aβ42-induced toxicity was found to correlate with stabilization of oligomers with a hydrodynamic radius (R[subscript H]) of 8−12 nm and attenuation of formation of oligomers with an R[subscript H] of 20−60 nm. In contrast, inhibition of Aβ42 paranucleus formation correlated with CTF solubility and the degree to which CTFs formed amyloid fibrils themselves but did not correlate with inhibition of Aβ42-induced toxicity. Our findings provide important insight into the mechanisms by which different CTFs inhibit the toxic effect of Aβ42 and suggest that stabilization of nontoxic Aβ42 oligomers is a promising strategy for designing inhibitors of Aβ42 neurotoxicity.en_US
dc.description.sponsorshipNational Institute on Aging (Grant AG027818)en_US
dc.language.isoen_US
dc.publisherAmerican Chemical Society (ACS)en_US
dc.relation.isversionofhttp://dx.doi.org/10.1021/bi100773gen_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourcePMCen_US
dc.titleMechanistic Investigation of the Inhibition of Aβ42 Assembly and Neurotoxicity by Aβ42 C-terminal Fragmentsen_US
dc.typeArticleen_US
dc.identifier.citationLi, Huiyuan et al. “Mechanistic Investigation of the Inhibition of Aβ42 Assembly and Neurotoxicity by Aβ42 C-Terminal Fragments.” Biochemistry 49.30 (2010): 6358–6364. © 2010 American Chemical Societyen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Physicsen_US
dc.contributor.mitauthorBenedek, George B.
dc.relation.journalBiochemistryen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsLi, Huiyuan; Monien, Bernhard H.; Lomakin, Aleksey; Zemel, Reeve; Fradinger, Erica A.; Tan, Miao; Spring, Sean M.; Urbanc, Brigita; Xie, Cui-Wei; Benedek, George B.; Bitan, Galen
dc.identifier.orcidhttps://orcid.org/0000-0003-2414-524X
mit.licensePUBLISHER_POLICYen_US


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