Journal Article

DZNE-2021-01524

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png LAG3 is not expressed in human and murine neurons and does not modulate α-synucleinopathies.

Emmenegger, M. ; De Cecco, E. ; Hruska-Plochan, M. ; Eninger, T.DZNE* ; Schneider, M. M. ; Barth, M.DZNE* ; Tantardini, E. ; de Rossi, P. ; Bacioglu, M.DZNE* ; Langston, R. G. ; Kaganovich, A. ; Bengoa-Vergniory, N. ; Gonzalez-Guerra, A. ; Avar, M. ; Heinzer, D. ; Reimann, R. ; Häsler, L. M.DZNE* ; Herling, T. W. ; Matharu, N. S. ; Landeck, N. ; Luk, K. ; Melki, R. ; Kahle, P. J.DZNE* ; Hornemann, S. ; Knowles, T. P. J. ; Cookson, M. R. ; Polymenidou, M. ; Jucker, M.DZNE* ; Aguzzi, A.

2021
EMBO Press Heidelberg

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Please use a persistent id in citations: doi:10.15252/emmm.202114745

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.

Keyword(s): Animals (MeSH) ; Humans (MeSH) ; Mice (MeSH) ; Mice, Transgenic (MeSH) ; Neurons (MeSH) ; Parkinson Disease (MeSH) ; Synucleinopathies (MeSH) ; alpha-Synuclein: genetics (MeSH) ; LAG3 ; neurodegeneration ; prionoids ; α-synuclein ; alpha-Synuclein

Note: (CC BY)

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Contributing Institute(s):

1. Cell Biology of Neurologic Diseases (AG Jucker)
2. Functional Neurogenetics (AG Kahle 2)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2021

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Database coverage:
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