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LAG3 is not expressed in human and murine neurons and does not modulate α-synucleinopathies

Emmenegger, M, De Cecco, E, Hruska-Plochan, M, Eininger, T, Schneider, MM, Barth, M, Tantardini, E, de Rossi, P, Langston, RG, Kaga-novich, A, Gonzalez-Guerra, A, Avar, M, Heinzer, D, Reimann, R, Häsler, LM, Herling, TW, Matharu, NS, Landeck, N, Luk, K, Melki, R, Kahle, PJ, Hornemann, S, Knowles, TP, Cookson, MR, Polymenidou, M, Jucker, M and Aguzzi, A (2021) LAG3 is not expressed in human and murine neurons and does not modulate α-synucleinopathies. EMBO Molecular Medicine. ISSN 17574684


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.

Item Type: Article
Keywords: LAG3 neurodegeneration prionoids α-synuclein
Date Deposited: 16 Sep 2021 00:45
Last Modified: 16 Sep 2021 00:45


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