{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lebœuf M"],"funding":["European Research Council","Association Nationale de la Recherche et de la Technologie"],"pagination":["e56525"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10398658"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["24(8)"],"pubmed_abstract":["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 α-motoneurons. Neutralizing extracellular ENGRAILED-1 by expressing a secreted single-chain antibody blocks its capture by spinal motoneurons resulting in α-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 α-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 α-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."],"journal":["EMBO reports"],"pubmed_title":["ENGRAILED-1 transcription factor has a paracrine neurotrophic activity on adult spinal α-motoneurons."],"pmcid":["PMC10398658"],"funding_grant_id":["2017/0488","339379"],"pubmed_authors":["Lebœuf M","Peze-Hedsieck E","Vargas-Abonce SE","Prochiantz A","Jimenez-Alonso L","Moya KL","Dupont E"],"additional_accession":[]},"is_claimable":false,"name":"ENGRAILED-1 transcription factor has a paracrine neurotrophic activity on adult spinal α-motoneurons.","description":"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 α-motoneurons. Neutralizing extracellular ENGRAILED-1 by expressing a secreted single-chain antibody blocks its capture by spinal motoneurons resulting in α-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 α-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 α-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.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Aug","modification":"2025-07-02T03:04:19.342Z","creation":"2025-04-06T17:46:03.623Z"},"accession":"S-EPMC10398658","cross_references":{"pubmed":["37534581"],"doi":["10.15252/embr.202256525"]}}