TY  - JOUR
AU  - Emmenegger, Marc
AU  - De Cecco, Elena
AU  - Hruska-Plochan, Marian
AU  - Eninger, Timo
AU  - Schneider, Matthias M
AU  - Barth, Melanie
AU  - Tantardini, Elena
AU  - de Rossi, Pierre
AU  - Bacioglu, Mehtap
AU  - Langston, Rebekah G
AU  - Kaganovich, Alice
AU  - Bengoa-Vergniory, Nora
AU  - Gonzalez-Guerra, Andrès
AU  - Avar, Merve
AU  - Heinzer, Daniel
AU  - Reimann, Regina
AU  - Häsler, Lisa M
AU  - Herling, Therese W
AU  - Matharu, Naunehal S
AU  - Landeck, Natalie
AU  - Luk, Kelvin
AU  - Melki, Ronald
AU  - Kahle, Philipp J
AU  - Hornemann, Simone
AU  - Knowles, Tuomas P J
AU  - Cookson, Mark R
AU  - Polymenidou, Magdalini
AU  - Jucker, Mathias
AU  - Aguzzi, Adriano
TI  - LAG3 is not expressed in human and murine neurons and does not modulate α-synucleinopathies.
JO  - EMBO molecular medicine
VL  - 13
IS  - 9
SN  - 1757-4684
CY  - Heidelberg
PB  - EMBO Press
M1  - DZNE-2021-01524
SP  - e14745
PY  - 2021
N1  - (CC BY)
AB  - 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.
KW  - Animals
KW  - Humans
KW  - Mice
KW  - Mice, Transgenic
KW  - Neurons
KW  - Parkinson Disease
KW  - Synucleinopathies
KW  - alpha-Synuclein: genetics
KW  - LAG3 (Other)
KW  - neurodegeneration (Other)
KW  - prionoids (Other)
KW  - α-synuclein (Other)
KW  - alpha-Synuclein (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:34309222
C2  - pmc:PMC8422075
DO  - DOI:10.15252/emmm.202114745
UR  - https://pub.dzne.de/record/162869
ER  -