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@ARTICLE{Emmenegger:162869,
author = {Emmenegger, Marc and De Cecco, Elena and Hruska-Plochan,
Marian and Eninger, Timo and Schneider, Matthias M and
Barth, Melanie and Tantardini, Elena and de Rossi, Pierre
and Bacioglu, Mehtap and Langston, Rebekah G and Kaganovich,
Alice and Bengoa-Vergniory, Nora and Gonzalez-Guerra,
Andrès and Avar, Merve and Heinzer, Daniel and Reimann,
Regina and Häsler, Lisa M and Herling, Therese W and
Matharu, Naunehal S and Landeck, Natalie and Luk, Kelvin and
Melki, Ronald and Kahle, Philipp J and Hornemann, Simone and
Knowles, Tuomas P J and Cookson, Mark R and Polymenidou,
Magdalini and Jucker, Mathias and Aguzzi, Adriano},
title = {{LAG}3 is not expressed in human and murine neurons and
does not modulate α-synucleinopathies.},
journal = {EMBO molecular medicine},
volume = {13},
number = {9},
issn = {1757-4684},
address = {Heidelberg},
publisher = {EMBO Press},
reportid = {DZNE-2021-01524},
pages = {e14745},
year = {2021},
note = {(CC BY)},
abstract = {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.},
keywords = {Animals / Humans / Mice / Mice, Transgenic / Neurons /
Parkinson Disease / Synucleinopathies / alpha-Synuclein:
genetics / LAG3 (Other) / neurodegeneration (Other) /
prionoids (Other) / α-synuclein (Other) / alpha-Synuclein
(NLM Chemicals)},
cin = {AG Jucker / AG Kahle 2},
ddc = {610},
cid = {I:(DE-2719)1210001 / I:(DE-2719)1210000-4},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34309222},
pmc = {pmc:PMC8422075},
doi = {10.15252/emmm.202114745},
url = {https://pub.dzne.de/record/162869},
}