| First Author | Lebœuf M | Year | 2023 |
| Journal | EMBO Rep | Volume | 24 |
| Issue | 8 | Pages | e56525 |
| PubMed ID | 37534581 | Mgi Jnum | J:338838 |
| Mgi Id | MGI:7516032 | Doi | 10.15252/embr.202256525 |
| Citation | Leboeuf M, et al. (2023) ENGRAILED-1 transcription factor has a paracrine neurotrophic activity on adult spinal alpha-motoneurons. EMBO Rep 24(8):e56525 |
| abstractText | Several homeoprotein transcription factors transfer between cells and regulate gene expression, protein translation, and chromatin organization in recipient cells. ENGRAILED-1 is one such homeoprotein expressed in spinal V1 interneurons that synapse on alpha-motoneurons. Neutralizing extracellular ENGRAILED-1 by expressing a secreted single-chain antibody blocks its capture by spinal motoneurons resulting in alpha-motoneuron loss and limb weakness. A similar but stronger phenotype is observed in the Engrailed-1 heterozygote mouse, confirming that ENGRAILED-1 exerts a paracrine neurotrophic activity on spinal cord alpha-motoneurons. Intrathecal injection of ENGRAILED-1 leads to its specific internalization by spinal motoneurons and has long-lasting protective effects against neurodegeneration and weakness. Midbrain dopaminergic neurons express Engrailed-1 and, similarly to spinal cord alpha-motoneurons, degenerate in the heterozygote. We identify genes expressed in spinal cord motoneurons whose expression changes in mouse Engrailed-1 heterozygote midbrain neurons. Among these, p62/SQSTM1 shows increased expression during aging in spinal cord motoneurons in the Engrailed-1 heterozygote and upon extracellular ENGRAILED-1 neutralization. We conclude that ENGRAILED-1 might regulate motoneuron aging and has non-cell-autonomous neurotrophic activity. |
