Publications

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

Published on July 26th, 2021

Authors: Marc Emmenegger, Elena De Cecco, Marian Hruska-Plochan, Timo Eninger, Matthias M Schneider, Melanie Barth, Elena Tantardini, Pierre de Rossi, Mehtap Bacioglu, Rebekah G Langston, Alice Kaganovich, Nora Bengoa-Vergniory, Andrès Gonzalez-Guerra, Merve Avar, Daniel Heinzer, Regina Reimann, Lisa M Häsler, Therese W Herling, Naunehal S Matharu, Natalie Landeck, Kelvin Luk, Ronald Melki, Philipp J Kahle, Simone Hornemann, Tuomas P J Knowles, Mark R Cookson, Magdalini Polymenidou, Mathias Jucker and Adriano Aguzzi

EMBO Mol. Med., 2021 13:e14745. 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.


InstrumentFluidity One-W
Therapeutic area: Covid-19

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