Show simple item record

dc.contributor.authorBergkvist, Liza
dc.contributor.authorRichards, Daniel R
dc.contributor.authorBernardo-Gancedo, Ana
dc.contributor.authorKumita, Janet R
dc.contributor.authorNilsson, Peter R
dc.contributor.authorBrorsson, Ann-Christin
dc.date.accessioned2020-03-10T00:30:18Z
dc.date.available2020-03-10T00:30:18Z
dc.date.issued2020
dc.identifier.issn1932-6203
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/303183
dc.description.abstractMany conflicting reports about the involvement of serum amyloid P component (SAP) in amyloid diseases have been presented over the years; SAP is known to be a universal component of amyloid aggregates but it has been suggested that it can both induce and suppress amyloid formation. By using our Drosophila model of systemic lysozyme amyloidosis, SAP has previously been shown to reduce the toxicity induced by the expression of the disease-associated lysozyme variant, F57I, in the Drosophila central nervous system. This study further investigates the involvement of SAP in modulating lysozyme toxicity using histochemistry and spectral analyses on the double transgenic WT and F57I lysozyme flies to probe; i) formation of aggregates, ii) morphological differences of the aggregated lysozyme species formed in the presence or absence of SAP, iii) location of lysozyme and iv) co-localisation of lysozyme and SAP in the fly brain. We found that SAP can counteract the toxicity (measured by the reduction in the median survival time) induced by F57I lysozyme by converting toxic F57I species into less toxic amyloid-like structures, as reflected by the spectral changes that p-FTAA undergoes when bound to lysozyme deposits in F57I-F57I-SAP flies as compared to F57I-F57I flies. Indeed, when SAP was introduced to in vitro lysozyme fibril formation, the endpoint fibrils had enhanced ThT fluorescence intensity as compared to lysozyme fibrils alone. This suggests that a general mechanism for SAP's role in amyloid diseases may be to promote the formation of stable, amyloid-like fibrils, thus decreasing the impact of toxic species formed along the aggregation pathway.
dc.format.mediumElectronic-eCollection
dc.languageeng
dc.publisherPublic Library of Science (PLoS)
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAnimals
dc.subjectAnimals, Genetically Modified
dc.subjectHumans
dc.subjectDrosophila melanogaster
dc.subjectAmyloidosis
dc.subjectDisease Models, Animal
dc.subjectAmyloid
dc.subjectMuramidase
dc.subjectSerum Amyloid P-Component
dc.subjectDrosophila Proteins
dc.subjectProtein Aggregates
dc.subjectProtein Aggregation, Pathological
dc.titleSerum amyloid P component promotes formation of distinct aggregated lysozyme morphologies and reduces toxicity in Drosophila flies expressing F57I lysozyme.
dc.typeArticle
prism.issueIdentifier1
prism.publicationDate2020
prism.publicationNamePLoS One
prism.startingPagee0227227
prism.volume15
dc.identifier.doi10.17863/CAM.50262
dcterms.dateAccepted2019-12-13
rioxxterms.versionofrecord10.1371/journal.pone.0227227
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2020-01-24
dc.contributor.orcidBrorsson, Ann-Christin [0000-0001-7651-3556]
dc.identifier.eissn1932-6203
rioxxterms.typeJournal Article/Review
cam.issuedOnline2020-01-24


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International