| First Author | Emmenegger M | Year | 2021 |
| Journal | EMBO Mol Med | Volume | 13 |
| Issue | 9 | Pages | e14745 |
| PubMed ID | 34309222 | Mgi Jnum | J:313403 |
| Mgi Id | MGI:6762220 | Doi | 10.15252/emmm.202114745 |
| Citation | Emmenegger M, et al. (2021) LAG3 is not expressed in human and murine neurons and does not modulate alpha-synucleinopathies. EMBO Mol Med 13(9):e14745 |
| abstractText | While the initial pathology of Parkinson's disease and other alpha-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 alpha-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 alpha-synuclein fibrils, the specificity of this interaction appears limited. Moreover, overexpression of LAG3 in cultured human neural cells did not cause any worsening of alpha-synuclein pathology ex vivo. The overall survival of A53T alpha-synuclein transgenic mice was unaffected by LAG3 depletion, and the seeded induction of alpha-synuclein lesions in hippocampal slice cultures was unaffected by LAG3 knockout. These data suggest that the proposed role of LAG3 in the spreading of alpha-synucleinopathies is not universally valid. |
