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LAG3 is not expressed in human and murine neurons and does not modulate α-synucleinopathies.

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cam.issuedOnline2021-07-26
dc.contributor.authorEmmenegger, Marc
dc.contributor.authorDe Cecco, Elena
dc.contributor.authorHruska-Plochan, Marian
dc.contributor.authorEninger, Timo
dc.contributor.authorSchneider, Matthias M
dc.contributor.authorBarth, Melanie
dc.contributor.authorTantardini, Elena
dc.contributor.authorde Rossi, Pierre
dc.contributor.authorBacioglu, Mehtap
dc.contributor.authorLangston, Rebekah G
dc.contributor.authorKaganovich, Alice
dc.contributor.authorBengoa-Vergniory, Nora
dc.contributor.authorGonzalez-Guerra, Andrès
dc.contributor.authorAvar, Merve
dc.contributor.authorHeinzer, Daniel
dc.contributor.authorReimann, Regina
dc.contributor.authorHäsler, Lisa M
dc.contributor.authorHerling, Therese W
dc.contributor.authorMatharu, Naunehal S
dc.contributor.authorLandeck, Natalie
dc.contributor.authorLuk, Kelvin
dc.contributor.authorMelki, Ronald
dc.contributor.authorKahle, Philipp J
dc.contributor.authorHornemann, Simone
dc.contributor.authorKnowles, Tuomas PJ
dc.contributor.authorCookson, Mark R
dc.contributor.authorPolymenidou, Magdalini
dc.contributor.authorJucker, Mathias
dc.contributor.authorAguzzi, Adriano
dc.contributor.orcidEmmenegger, Marc [0000-0002-6073-8811]
dc.contributor.orcidDe Cecco, Elena [0000-0002-0148-2596]
dc.contributor.orcidHruska-Plochan, Marian [0000-0002-9253-4362]
dc.contributor.orcidSchneider, Matthias M [0000-0002-1894-1859]
dc.contributor.orcidTantardini, Elena [0000-0001-9189-3390]
dc.contributor.orcidBacioglu, Mehtap [0000-0003-0304-7026]
dc.contributor.orcidBengoa-Vergniory, Nora [0000-0002-3700-0464]
dc.contributor.orcidAvar, Merve [0000-0003-4665-5558]
dc.contributor.orcidHeinzer, Daniel [0000-0002-3282-4042]
dc.contributor.orcidLandeck, Natalie [0000-0002-8399-4009]
dc.contributor.orcidLuk, Kelvin [0000-0002-6591-6269]
dc.contributor.orcidMelki, Ronald [0000-0003-0000-7096]
dc.contributor.orcidHornemann, Simone [0000-0002-2674-9891]
dc.contributor.orcidCookson, Mark R [0000-0002-1058-3831]
dc.contributor.orcidJucker, Mathias [0000-0001-9045-1072]
dc.contributor.orcidAguzzi, Adriano [0000-0002-0344-6708]
dc.date.accessioned2021-09-24T23:30:37Z
dc.date.available2021-09-24T23:30:37Z
dc.date.issued2021-09-07
dc.description.abstractWhile the initial pathology of Parkinson's disease and other α-synucleinopathies is often confined to circumscribed brain regions, it can spread and progressively affect adjacent and distant brain locales. This process may be controlled by cellular receptors of α-synuclein fibrils, one of which was proposed to be the LAG3 immune checkpoint molecule. Here, we analysed the expression pattern of LAG3 in human and mouse brains. Using a variety of methods and model systems, we found no evidence for LAG3 expression by neurons. While we confirmed that LAG3 interacts with α-synuclein fibrils, the specificity of this interaction appears limited. Moreover, overexpression of LAG3 in cultured human neural cells did not cause any worsening of α-synuclein pathology ex vivo. The overall survival of A53T α-synuclein transgenic mice was unaffected by LAG3 depletion, and the seeded induction of α-synuclein lesions in hippocampal slice cultures was unaffected by LAG3 knockout. These data suggest that the proposed role of LAG3 in the spreading of α-synucleinopathies is not universally valid.
dc.format.mediumPrint-Electronic
dc.identifier.doi10.17863/CAM.75956
dc.identifier.eissn1757-4684
dc.identifier.issn1757-4676
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/328508
dc.languageeng
dc.language.isoeng
dc.publisherSpringer Science and Business Media LLC
dc.publisher.urlhttp://dx.doi.org/10.15252/emmm.202114745
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectLAG3
dc.subjectneurodegeneration
dc.subjectprionoids
dc.subjectα-synuclein
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectMice, Transgenic
dc.subjectNeurons
dc.subjectParkinson Disease
dc.subjectSynucleinopathies
dc.subjectalpha-Synuclein
dc.titleLAG3 is not expressed in human and murine neurons and does not modulate α-synucleinopathies.
dc.typeArticle
dcterms.dateAccepted2021-07-06
prism.issueIdentifier9
prism.publicationDate2021
prism.publicationNameEMBO Mol Med
prism.startingPagee14745
prism.volume13
pubs.funder-project-idEuropean Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (674979)
pubs.funder-project-idMedical Research Council (MR/M024962/1)
pubs.funder-project-idMedical Research Council (MR/L023784/2)
rioxxterms.licenseref.startdate2021-09
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionVoR
rioxxterms.versionofrecord10.15252/emmm.202114745

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