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

Autor: Emmenegger, Marc, De Cecco, Elena, Hruska-Plochan, Marian, Eninger, Timo, Schneider, Matthias M, Barth, Melanie, Tantardini, Elena, De Rossi, Pierre, Bacioglu, Mehtap, Langston, Rebekah G, Kaganovich, Alice, Bengoa-Vergniory, Nora, Gonzalez-Guerra, Andrès, Avar, Merve, Heinzer, Daniel, Reimann, Regina, Häsler, Lisa M, Herling, Therese W, Matharu, Naunehal S, Landeck, Natalie, Luk, Kelvin, Melki, Ronald, Kahle, Philipp J, Hornemann, Simone, Knowles, Tuomas PJ, Cookson, Mark R, Polymenidou, Magdalini, Jucker, Mathias, Aguzzi, Adriano
Přispěvatelé: 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 [Oxford], Penn Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Centre National de la Recherche Scientifique (CNRS)-Service MIRCEN (MIRCEN), 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-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)-Université Paris-Saclay, 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, University of Oxford, Service MIRCEN (MIRCEN), 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)-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), Emmenegger, Marc [0000-0002-6073-8811], De Cecco, Elena [0000-0002-0148-2596], Hruska-Plochan, Marian [0000-0002-9253-4362], Schneider, Matthias M [0000-0002-1894-1859], Tantardini, Elena [0000-0001-9189-3390], Bacioglu, Mehtap [0000-0003-0304-7026], Bengoa-Vergniory, Nora [0000-0002-3700-0464], Avar, Merve [0000-0003-4665-5558], Heinzer, Daniel [0000-0002-3282-4042], Landeck, Natalie [0000-0002-8399-4009], Luk, Kelvin [0000-0002-6591-6269], Melki, Ronald [0000-0003-0000-7096], Hornemann, Simone [0000-0002-2674-9891], Cookson, Mark R [0000-0002-1058-3831], Jucker, Mathias [0000-0001-9045-1072], Aguzzi, Adriano [0000-0002-0344-6708], Apollo - University of Cambridge Repository, Hruska‐Plochan, Marian [0000-0002-9253-4362], Bengoa‐Vergniory, Nora [0000-0002-3700-0464], University of Zurich, Aguzzi, Adriano
Rok vydání: 2021
Předmět:
Zdroj: EMBO Molecular Medicine
EMBO Molecular Medicine, Wiley Open Access, 2021, pp.e14745. ⟨10.15252/emmm.202114745⟩
EMBO Molecular Medicine, 2021, pp.e14745. ⟨10.15252/emmm.202114745⟩
EMBO Molecular Medicine, Vol 13, Iss 9, Pp n/a-n/a (2021)
EMBO molecular medicine 13(9), e14745 (2021). doi:10.15252/emmm.202114745
ISSN: 1757-4676
1757-4684
DOI: 10.17863/cam.73376
Popis: Funder: University of Zurich and University Hospital of Zurich
Funder: NOMIS Stiftung (NOMIS Foundation); Id: http://dx.doi.org/10.13039/501100008483
Funder: Forschungskredit University of Zurich
While 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.
Databáze: OpenAIRE
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