LAG3 is not expressed in human and murine neurons and does not modulate α-synucleinopathies.
de Rossi, Pierre
Langston, Rebekah G
Häsler, Lisa M
Matharu, Naunehal S
Kahle, Philipp J
EMBO Mol Med
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Emmenegger, M., De Cecco, E., Hruska-Plochan, M., Eninger, T., Schneider, M., Barth, M., Tantardini, E., et al. (2021). LAG3 is not expressed in human and murine neurons and does not modulate α-synucleinopathies.. EMBO Mol Med, 13 (9), e14745. https://doi.org/10.15252/emmm.202114745
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.
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (674979)
Medical Research Council (MR/M024962/1)
External DOI: https://doi.org/10.15252/emmm.202114745
This record's URL: https://www.repository.cam.ac.uk/handle/1810/328508
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/