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A New Zebrafish Model to Measure Neuronal α-Synuclein Clearance In Vivo.

cam.issuedOnline2022-05-12
dc.contributor.authorLopez, Ana
dc.contributor.authorGorb, Alena
dc.contributor.authorPalha, Nuno
dc.contributor.authorFleming, Angeleen
dc.contributor.authorRubinsztein, David C
dc.contributor.orcidFleming, Angeleen [0000-0003-3721-7126]
dc.date.accessioned2022-06-29T19:47:46Z
dc.date.available2022-06-29T19:47:46Z
dc.date.issued2022-05-12
dc.date.updated2022-06-29T19:47:45Z
dc.description.abstractThe accumulation and aggregation of α-synuclein (α-SYN) is a common characteristic of synucleinopathies, such as Parkinson's Disease (PD), Dementia with Lewy Bodies (DLB) or Multiple System Atrophy (MSA). Multiplications of the wildtype gene of α-SYN (SNCA) and most point mutations make α-SYN more aggregate-prone, and are associated with mitochondrial defects, trafficking obstruction, and impaired proteostasis, which contribute to elevated neuronal death. Here, we present new zebrafish models expressing either human wildtype (wt), or A53T mutant, α-SYN that recapitulate the above-mentioned hallmarks of synucleinopathies. The appropriate clearance of toxic α-SYN has been previously shown to play a key role in maintaining cell homeostasis and survival. However, the paucity of models to investigate α-SYN degradation in vivo limits our understanding of this process. Based on our recently described imaging method for measuring tau protein clearance in neurons in living zebrafish, we fused human SNCA to the photoconvertible protein Dendra2 which enabled analyses of wt and A53T α-SYN clearance kinetics in vivo. Moreover, these zebrafish models can be used to investigate the kinetics of α-SYN aggregation and to study the mechanisms, and potential new targets, controlling the clearance of both soluble and aggregated α-SYN.
dc.description.sponsorshipFunding for this study was obtained from Servier and the UK Dementia Research Institute (funded by the MRC, Alzheimer’s Research UK and the Alzheimer’s Society). European Union’s Horizon 2020 Framework research and innovation program under the Marie Skłodowska-Curie Grant Number 746509 and Guarantors of Brain Non-Clinical Post - Doctoral Fellowship (to S.D.T).
dc.identifier.doi10.17863/CAM.85961
dc.identifier.eissn2073-4425
dc.identifier.issn2073-4425
dc.identifier.other35627253
dc.identifier.otherPMC9141618
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/338548
dc.languageeng
dc.language.isoeng
dc.publisherMDPI AG
dc.publisher.urlhttp://dx.doi.org/10.3390/genes13050868
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 2073-4425
dc.sourcenlmid: 101551097
dc.subjectParkinson’s disease
dc.subjectaggregation
dc.subjectautophagy
dc.subjectaxonal transport
dc.subjectneurodegeneration
dc.subjectprotein clearance
dc.subjectzebrafish disease model
dc.subjectα-synuclein
dc.subjectAnimals
dc.subjectKinetics
dc.subjectNeurons
dc.subjectSynucleinopathies
dc.subjectZebrafish
dc.subjectalpha-Synuclein
dc.titleA New Zebrafish Model to Measure Neuronal α-Synuclein Clearance In Vivo.
dc.typeArticle
dcterms.dateAccepted2022-05-05
prism.issueIdentifier5
prism.publicationNameGenes (Basel)
prism.volume13
pubs.funder-project-idEuropean Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (746509)
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.3390/genes13050868

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