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Stabilization and Characterization of Cytotoxic Aβ40 Oligomers Isolated from an Aggregation Reaction in the Presence of Zinc Ions.

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cam.issuedOnline2018-08-10
dc.contributor.authorMannini, Benedetta
dc.contributor.authorHabchi, Johnny
dc.contributor.authorChia, Sean
dc.contributor.authorRuggeri, Francesco S
dc.contributor.authorPerni, Michele
dc.contributor.authorKnowles, Tuomas PJ
dc.contributor.authorDobson, Christopher M
dc.contributor.authorVendruscolo, Michele
dc.contributor.orcidPerni, Michele [0000-0001-7593-8376]
dc.contributor.orcidKnowles, Tuomas PJ [0000-0002-7879-0140]
dc.contributor.orcidVendruscolo, Michele [0000-0002-3616-1610]
dc.date.accessioned2018-11-01T14:01:52Z
dc.date.available2018-11-01T14:01:52Z
dc.date.issued2018-12-19
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.identifier.doi10.17863/CAM.31851
dc.identifier.eissn1948-7193
dc.identifier.issn1948-7193
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/284475
dc.languageeng
dc.language.isoeng
dc.publisherAmerican Chemical Society (ACS)
dc.publisher.urlhttp://dx.doi.org/10.1021/acschemneuro.8b00141
dc.subjectAlzheimer’s disease
dc.subjectOC-positive aggregates
dc.subjectProtein oligomer aggregates
dc.subjectamyloid
dc.subjectantiparallel oligomer
dc.subjectmetal ions
dc.subjectAlzheimer Disease
dc.subjectAmyloid beta-Peptides
dc.subjectAnimals
dc.subjectCaenorhabditis elegans
dc.subjectCell Line, Tumor
dc.subjectCell Survival
dc.subjectHumans
dc.subjectIn Vitro Techniques
dc.subjectMovement
dc.subjectNeuroblastoma
dc.subjectNeurons
dc.subjectPeptide Fragments
dc.subjectPolymers
dc.subjectProtein Aggregates
dc.subjectProtein Aggregation, Pathological
dc.subjectProtein Conformation, beta-Strand
dc.subjectZinc
dc.titleStabilization and Characterization of Cytotoxic Aβ40 Oligomers Isolated from an Aggregation Reaction in the Presence of Zinc Ions.
dc.typeArticle
dcterms.dateAccepted2018-07-10
prism.endingPage2971
prism.issueIdentifier12
prism.publicationDate2018
prism.publicationNameACS Chem Neurosci
prism.startingPage2959
prism.volume9
rioxxterms.licenseref.startdate2018-12
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionAM
rioxxterms.versionofrecord10.1021/acschemneuro.8b00141

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