| First Author | Mao X | Year | 2024 |
| Journal | Nat Commun | Volume | 15 |
| Issue | 1 | Pages | 4663 |
| PubMed ID | 38821932 | Mgi Jnum | J:349362 |
| Mgi Id | MGI:7646414 | Doi | 10.1038/s41467-024-49016-3 |
| Citation | Mao X, et al. (2024) Aplp1 interacts with Lag3 to facilitate transmission of pathologic alpha-synuclein. Nat Commun 15(1):4663 |
| abstractText | Pathologic alpha-synuclein (alpha-syn) spreads from cell-to-cell, in part, through binding to the lymphocyte-activation gene 3 (Lag3). Here we report that amyloid beta precursor-like protein 1 (Aplp1) interacts with Lag3 that facilitates the binding, internalization, transmission, and toxicity of pathologic alpha-syn. Deletion of both Aplp1 and Lag3 eliminates the loss of dopaminergic neurons and the accompanying behavioral deficits induced by alpha-syn preformed fibrils (PFF). Anti-Lag3 prevents the internalization of alpha-syn PFF by disrupting the interaction of Aplp1 and Lag3, and blocks the neurodegeneration induced by alpha-syn PFF in vivo. The identification of Aplp1 and the interplay with Lag3 for alpha-syn PFF induced pathology deepens our insight about molecular mechanisms of cell-to-cell transmission of pathologic alpha-syn and provides additional targets for therapeutic strategies aimed at preventing neurodegeneration in Parkinson's disease and related alpha-synucleinopathies. |
