LAG3 is not expressed in human and murine neurons and does not modulate α‐synucleinopathies
In: ISSN: 1757-4676, 2021
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academicJournal
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International audience ; While the initial pathology of Parkinson's disease and other αsynucleinopathies 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 αsynuclein 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 αsynuclein 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.
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LAG3 is not expressed in human and murine neurons and does not modulate α‐synucleinopathies
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| Autor/in / Beteiligte Person: | Emmenegger, Marc ; de Cecco, Elena ; Hruska‐plochan, Marian ; Eninger, Timo ; Schneider, Matthias ; Barth, Melanie ; Tantardini, Elena ; de Rossi, Pierre ; Bacioglu, Mehtap ; Langston, Rebekah ; Kaganovich, Alice ; Bengoa‐vergniory, Nora ; Gonzalez‐guerra, Andrès ; Avar, Merve ; Heinzer, Daniel ; Reimann, Regina ; Häsler, Lisa ; Herling, Therese ; Matharu, Naunehal ; Landeck, Natalie ; Luk, Kelvin ; Melki, Ronald ; Kahle, Philipp ; Hornemann, Simone ; Knowles, Tuomas ; Cookson, Mark ; Polymenidou, Magdalini ; Jucker, Mathias ; Aguzzi, Adriano ; Universität Zürich Zürich = University of Zurich (UZH) ; German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) ; University of Cambridge UK (CAM) ; National Institutes of Health Bethesda (NIH) ; University of Oxford ; Penn Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA ; Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN) ; Service MIRCEN (MIRCEN) ; Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB) ; Direction de Recherche Fondamentale (CEA) (DRF (CEA)) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS) ; University of Tübingen ; National Centre for Competence in Research (NCCR) RNA & Disease (51NF40-182880) ; European Project: 670958,H2020,ERC-2014-ADG,PRION2020(2015) ; European Project: 674979,H2020,H2020-MSCA-ITN-2015,NANOTRANS(2016) ; European Project: (grant No 116060),IMPRiND |
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| Zeitschrift: | ISSN: 1757-4676, 2021 |
| Veröffentlichung: | HAL CCSD ; Wiley Open Access, 2021 |
| Medientyp: | academicJournal |
| DOI: | 10.15252/emmm.202114745 |
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