biostudies-otherUnknownMarc EmmeneggerNOMIS Stiftung (NOMIS Foundation)EU Horizon 2020University of Zurich and University Hospital of ZurichEU/EFPIA/Innovative Medicines Initiative 2 Joint UndertakingEuropean Research Council (ERC)Forschungskredit University of ZurichNational Centre for Competence in Research (NCCR)Swiss Personalized Health NetworkSwiss National Science Foundation Project GrantEMBO Molecular Medicinehttps://www.ebi.ac.uk/biostudies/studies/S-SCDT-EMM-2021-14745While the initial pathology of Parkinson's disease and other ?-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 ?-synuclein fibrils, one of which was proposed to be the LAG3 immune checkpoint molecule. Here, we analyzed 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 ?-synuclein fibrils, the specificity of this interaction appears limited. Moreover, overexpression of LAG3 in cultured human neural cells did not cause any worsening of ?-synuclein pathology ex vivo. The overall survival of A53T biostudies-otherPhysProt51NF40-1828802017DRI17ETN grant 674979-Nanotrans116060ERC Prion2020310030_192650Dr. Alice KaganovichDr. Timo EningerDr. Mathias JuckerMs. Therese, W. HerlingKelvin, C LukMr. Naunehal, S. MatharuProf. Philipp, J. KahleAndrés Gonzalez-GuerraDr. Elena De CeccoDr. Marian Hruska-PlochanMr. Daniel HeinzerDr. Lisa, M. HäslerDr. Pierre de RossiMs. Melanie BarthDr. Nora Bengoa-VergnioryMs. Elena TantardiniProf. Adriano AguzziTuomas, P. KnowlesMr. Matthias, M. SchneiderProf. Magdalini PolymenidouDr. Ronald MelkiMerve AvarRegina ReimannMs. Natalie LandeckDr. Mehtap BaciogluDr. Rebekah, G. LangstonDr. Simone HornemannMark, R CooksonMarc EmmeneggerfalseLAG3 is not expressed in human and murine neurons and does not modulate ?-synucleinopathiesWhile the initial pathology of Parkinson's disease and other ?-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 ?-synuclein fibrils, one of which was proposed to be the LAG3 immune checkpoint molecule. Here, we analyzed 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 ?-synuclein fibrils, the specificity of this interaction appears limited. Moreover, overexpression of LAG3 in cultured human neural cells did not cause any worsening of ?-synuclein pathology ex vivo. The overall survival of A53T 2021-10-14T00:00:00Z2021-10-14T14:21:42Z2021-10-14T14:21:42ZS-SCDT-EMM-2021-1474510.15252/emmm.202114745