%0 Journal Article
%A Emmenegger, Marc
%A De Cecco, Elena
%A Hruska-Plochan, Marian
%A Eninger, Timo
%A Schneider, Matthias M
%A Barth, Melanie
%A Tantardini, Elena
%A de Rossi, Pierre
%A Bacioglu, Mehtap
%A Langston, Rebekah G
%A Kaganovich, Alice
%A Bengoa-Vergniory, Nora
%A Gonzalez-Guerra, Andrès
%A Avar, Merve
%A Heinzer, Daniel
%A Reimann, Regina
%A Häsler, Lisa M
%A Herling, Therese W
%A Matharu, Naunehal S
%A Landeck, Natalie
%A Luk, Kelvin
%A Melki, Ronald
%A Kahle, Philipp J
%A Hornemann, Simone
%A Knowles, Tuomas P J
%A Cookson, Mark R
%A Polymenidou, Magdalini
%A Jucker, Mathias
%A Aguzzi, Adriano
%T LAG3 is not expressed in human and murine neurons and does not modulate α-synucleinopathies.
%J EMBO molecular medicine
%V 13
%N 9
%@ 1757-4684
%C Heidelberg
%I EMBO Press
%M DZNE-2021-01524
%P e14745
%D 2021
%Z (CC BY)
%X 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.
%K Animals
%K Humans
%K Mice
%K Mice, Transgenic
%K Neurons
%K Parkinson Disease
%K Synucleinopathies
%K alpha-Synuclein: genetics
%K LAG3 (Other)
%K neurodegeneration (Other)
%K prionoids (Other)
%K α-synuclein (Other)
%K alpha-Synuclein (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:34309222
%2 pmc:PMC8422075
%R 10.15252/emmm.202114745
%U https://pub.dzne.de/record/162869