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dc.contributor.authorMeisl, Georgen
dc.contributor.authorKurt, Timothyen
dc.contributor.authorCondado-Morales, Itzelen
dc.contributor.authorBett, Cyrusen
dc.contributor.authorSorce, Silviaen
dc.contributor.authorNuvolone, Marioen
dc.contributor.authorMichaels, Thomasen
dc.contributor.authorHeinzer, Danielen
dc.contributor.authorAvar, Merveen
dc.contributor.authorCohen, Samuel IAen
dc.contributor.authorHornemann, Simoneen
dc.contributor.authorAguzzi, Adrianoen
dc.contributor.authorDobson, Christopher Men
dc.contributor.authorSigurdson, Christina Jen
dc.contributor.authorKnowles, Tuomasen
dc.date.accessioned2021-02-15T11:37:43Z
dc.date.available2021-02-15T11:37:43Z
dc.date.issued2021-04en
dc.identifier.issn1545-9993
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/317625
dc.description.abstractPrions consist of pathological assemblies of normal cellular prion protein and cause infectious neurodegenerative diseases, a phenomenon mirrored in many other prion-like neurodegenerative diseases. However, despite their key importance in disease, the individual processes governing this formation of pathogenic aggregates, as well as their rates, have remained challenging to elucidate in vivo. Here we bring together a mathematical framework with kinetics of the accumulation of prions in mice and microfluidic measurements of aggregate size to dissect the overall aggregation reaction into its constituent processes and quantify the reaction rates in mice. Taken together, the data show that multiplication of prions in vivo is slower than in in vitro experiments, but efficient when compared to other amyloid systems, and displays scaling behaviour characteristic of aggregate fragmentation. These results provide a framework for the determination of the mechanisms of disease-associated aggregation processes within living organisms.
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherNature Research
dc.rightsAll rights reserved
dc.rights.uri
dc.subjectAnimalsen
dc.subjectHumansen
dc.subjectMiceen
dc.subjectParkinson Diseaseen
dc.subjectAlzheimer Diseaseen
dc.subjectAmyloiden
dc.subjectPrionsen
dc.subjectModels, Theoreticalen
dc.subjectProtein Aggregation, Pathologicalen
dc.titleScaling analysis reveals the mechanism and rates of prion replication in vivo.en
dc.typeArticle
prism.endingPage372
prism.issueIdentifier4en
prism.publicationDate2021en
prism.publicationNameNature structural & molecular biologyen
prism.startingPage365
prism.volume28en
dc.identifier.doi10.17863/CAM.64741
dcterms.dateAccepted2021-01-26en
rioxxterms.versionofrecord10.1038/s41594-021-00565-xen
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2021-04en
dc.contributor.orcidMeisl, Georg [0000-0002-6562-7715]
dc.contributor.orcidCondado-Morales, Itzel [0000-0001-7592-4556]
dc.contributor.orcidBett, Cyrus [0000-0001-9820-9686]
dc.contributor.orcidMichaels, Thomas [0000-0001-6931-5041]
dc.contributor.orcidHeinzer, Daniel [0000-0002-3282-4042]
dc.contributor.orcidHornemann, Simone [0000-0002-2674-9891]
dc.contributor.orcidAguzzi, Adriano [0000-0002-0344-6708]
dc.contributor.orcidSigurdson, Christina J [0000-0002-1770-0965]
dc.contributor.orcidKnowles, Tuomas [0000-0002-7879-0140]
dc.identifier.eissn1545-9985
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idEuropean Research Council (337969)
cam.orpheus.successMon Apr 12 07:31:07 BST 2021 - Embargo updated*
cam.orpheus.counter7*
rioxxterms.freetoread.startdate2021-09-25


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