Open AccessLAG3 is not expressed in human and murine neurons and does not modulate α‐synucleinopathies
Author(s) -
Emmenegger Marc,
De Cecco Elena,
HruskaPlochan Marian,
Eninger Timo,
Schneider Matthias M,
Barth Melanie,
Tantardini Elena,
de Rossi Pierre,
Bacioglu Mehtap,
Langston Rebekah G,
Kaganovich Alice,
BengoaVergniory Nora,
GonzalezGuerra Andrès,
Avar Merve,
Heinzer Daniel,
Reimann Regina,
Häsler Lisa M,
Herling Therese W,
Matharu Naunehal S,
Landeck Natalie,
Luk Kelvin,
Melki Ronald,
Kahle Philipp J,
Hornemann Simone,
Knowles Tuomas P J,
Cookson Mark R,
Polymenidou Magdalini,
Jucker Mathias,
Aguzzi Adriano
Publication year - 2021
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.202114745
Subject(s) - synucleinopathies , biology , neuroscience , microbiology and biotechnology , genetically modified mouse , ex vivo , hippocampal formation , transgene , alpha synuclein , in vivo , pathology , parkinson's disease , disease , medicine , biochemistry , gene
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.