EMBO Molecular Medicine (Sep 2021)
LAG3 is not expressed in human and murine neurons and does not modulate α‐synucleinopathies
- 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,
- Adriano Aguzzi
Affiliations
- Marc Emmenegger
- Institute of Neuropathology University of Zurich Zurich Switzerland
- Elena De Cecco
- Institute of Neuropathology University of Zurich Zurich Switzerland
- Marian Hruska‐Plochan
- Department of Quantitative Biomedicine University of Zurich Zurich Switzerland
- Timo Eninger
- German Center for Neurodegenerative Diseases (DZNE) Tübingen Germany
- Matthias M Schneider
- Yusuf Hamied Department of Chemistry Centre for Misfolding Diseases University of Cambridge Cambridge UK
- Melanie Barth
- German Center for Neurodegenerative Diseases (DZNE) Tübingen Germany
- Elena Tantardini
- Department of Quantitative Biomedicine University of Zurich Zurich Switzerland
- Pierre de Rossi
- Department of Quantitative Biomedicine University of Zurich Zurich Switzerland
- Mehtap Bacioglu
- German Center for Neurodegenerative Diseases (DZNE) Tübingen Germany
- Rebekah G Langston
- Cell Biology and Gene Expression Section Laboratory of Neurogenetics National Institute on Aging National Institutes of Health Bethesda MD USA
- Alice Kaganovich
- Cell Biology and Gene Expression Section Laboratory of Neurogenetics National Institute on Aging National Institutes of Health Bethesda MD USA
- Nora Bengoa‐Vergniory
- Department of Physiology, Anatomy and Genetics Oxford Parkinson’s Disease Center (OPDC) Oxford University Oxford UK
- Andrès Gonzalez‐Guerra
- Institute of Neuropathology University of Zurich Zurich Switzerland
- Merve Avar
- Institute of Neuropathology University of Zurich Zurich Switzerland
- Daniel Heinzer
- Institute of Neuropathology University of Zurich Zurich Switzerland
- Regina Reimann
- Institute of Neuropathology University of Zurich Zurich Switzerland
- Lisa M Häsler
- German Center for Neurodegenerative Diseases (DZNE) Tübingen Germany
- Therese W Herling
- Yusuf Hamied Department of Chemistry Centre for Misfolding Diseases University of Cambridge Cambridge UK
- Naunehal S Matharu
- Yusuf Hamied Department of Chemistry Centre for Misfolding Diseases University of Cambridge Cambridge UK
- Natalie Landeck
- Cell Biology and Gene Expression Section Laboratory of Neurogenetics National Institute on Aging National Institutes of Health Bethesda MD USA
- Kelvin Luk
- Department of Pathology and Laboratory Medicine and Center for Neurodegenerative Disease Research University of Pennsylvania Perelman School of Medicine Philadelphia PA USA
- Ronald Melki
- Laboratory of Neurodegenerative Diseases CNRS Institut François Jacob (MIRCen) CEA Fontenay‐aux‐Roses France
- Philipp J Kahle
- German Center for Neurodegenerative Diseases (DZNE) Tübingen Germany
- Simone Hornemann
- Institute of Neuropathology University of Zurich Zurich Switzerland
- Tuomas P J Knowles
- Yusuf Hamied Department of Chemistry Centre for Misfolding Diseases University of Cambridge Cambridge UK
- Mark R Cookson
- Cell Biology and Gene Expression Section Laboratory of Neurogenetics National Institute on Aging National Institutes of Health Bethesda MD USA
- Magdalini Polymenidou
- Department of Quantitative Biomedicine University of Zurich Zurich Switzerland
- Mathias Jucker
- German Center for Neurodegenerative Diseases (DZNE) Tübingen Germany
- Adriano Aguzzi
- Institute of Neuropathology University of Zurich Zurich Switzerland
- DOI
- https://doi.org/10.15252/emmm.202114745
- Journal volume & issue
-
Vol. 13,
no. 9
pp. n/a – n/a
Abstract
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.
Keywords
