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dc.contributor.authorMannini, Benedetta
dc.contributor.authorHabchi, Johnny
dc.contributor.authorChia, Sean Keng Rui
dc.contributor.authorRuggeri, Francesco
dc.contributor.authorPerni, Michele
dc.contributor.authorKnowles, Tuomas
dc.contributor.authorDobson, Christopher
dc.contributor.authorVendruscolo, Michele
dc.date.accessioned2018-11-01T14:01:52Z
dc.date.available2018-11-01T14:01:52Z
dc.date.issued2018-12-19
dc.identifier.issn1948-7193
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/284475
dc.description.abstractSmall oligomers formed during the aggregation of certain peptides and proteins are highly cytotoxic in numerous neurodegenerative disorders. Because of their transient nature and conformational heterogeneity, however, the structural and biological features of these oligomers are still poorly understood. Here, we describe a method of generating stable oligomers formed by the Alzheimer's Aβ40 peptide by carrying out an aggregation reaction in the presence of zinc ions. The resulting oligomers are amenable to detailed biophysical and biological characterization, which reveals a homogeneous population with small size, high cross-β sheet structure content, and extended hydrophobic surface patches. We also show that these oligomers decrease the viability of neuroblastoma cells and impair the motility of C. elegans. The availability of these oligomers offers novel opportunities for studying the mechanisms of Aβ40 toxicity in vitro and in cellular and animal models of Alzheimer's disease.
dc.description.sponsorshipSwiss National Science Foundation for Science (grant number P2ELP2_162116)
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherAmerican Chemical Society (ACS)
dc.subjectNeurons
dc.subjectCell Line, Tumor
dc.subjectAnimals
dc.subjectHumans
dc.subjectCaenorhabditis elegans
dc.subjectNeuroblastoma
dc.subjectAlzheimer Disease
dc.subjectZinc
dc.subjectPolymers
dc.subjectPeptide Fragments
dc.subjectCell Survival
dc.subjectMovement
dc.subjectAmyloid beta-Peptides
dc.subjectIn Vitro Techniques
dc.subjectProtein Aggregates
dc.subjectProtein Aggregation, Pathological
dc.subjectProtein Conformation, beta-Strand
dc.titleStabilization and Characterization of Cytotoxic Aβ40 Oligomers Isolated from an Aggregation Reaction in the Presence of Zinc Ions.
dc.typeArticle
prism.endingPage2971
prism.issueIdentifier12
prism.publicationDate2018
prism.publicationNameACS Chem Neurosci
prism.startingPage2959
prism.volume9
dc.identifier.doi10.17863/CAM.31851
dcterms.dateAccepted2018-07-10
rioxxterms.versionofrecord10.1021/acschemneuro.8b00141
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-12
dc.contributor.orcidMannini, Benedetta [0000-0001-6812-7348]
dc.contributor.orcidChia, Sean Keng Rui [0000-0001-8905-8695]
dc.contributor.orcidRuggeri, Francesco [0000-0002-1232-1907]
dc.contributor.orcidPerni, Michele [0000-0001-7593-8376]
dc.contributor.orcidKnowles, Tuomas [0000-0002-7879-0140]
dc.contributor.orcidVendruscolo, Michele [0000-0002-3616-1610]
dc.identifier.eissn1948-7193
rioxxterms.typeJournal Article/Review
cam.issuedOnline2018-07-09
rioxxterms.freetoread.startdate2019-08-10


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