CXCL12α/SDF‐1 from perisynaptic Schwann cells promotes regeneration of injured motor axon terminals
Abstract The neuromuscular junction has retained through evolution the capacity to regenerate after damage, but little is known on the inter‐cellular signals involved in its functional recovery from trauma, autoimmune attacks, or neurotoxins. We report here that CXCL12α, also abbreviated as stromal‐...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2017-08-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.201607257 |
| _version_ | 1797279823938191360 |
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| author | Samuele Negro Francesca Lessi Elisa Duregotti Paolo Aretini Marco La Ferla Sara Franceschi Michele Menicagli Elisanna Bergamin Egle Radice Marcus Thelen Aram Megighian Marco Pirazzini Chiara M Mazzanti Michela Rigoni Cesare Montecucco |
| author_facet | Samuele Negro Francesca Lessi Elisa Duregotti Paolo Aretini Marco La Ferla Sara Franceschi Michele Menicagli Elisanna Bergamin Egle Radice Marcus Thelen Aram Megighian Marco Pirazzini Chiara M Mazzanti Michela Rigoni Cesare Montecucco |
| author_sort | Samuele Negro |
| collection | DOAJ |
| description | Abstract The neuromuscular junction has retained through evolution the capacity to regenerate after damage, but little is known on the inter‐cellular signals involved in its functional recovery from trauma, autoimmune attacks, or neurotoxins. We report here that CXCL12α, also abbreviated as stromal‐derived factor‐1 (SDF‐1), is produced specifically by perisynaptic Schwann cells following motor axon terminal degeneration induced by α‐latrotoxin. CXCL12α acts via binding to the neuronal CXCR4 receptor. A CXCL12α‐neutralizing antibody or a specific CXCR4 inhibitor strongly delays recovery from motor neuron degeneration in vivo. Recombinant CXCL12α in vivo accelerates neurotransmission rescue upon damage and very effectively stimulates the axon growth of spinal cord motor neurons in vitro. These findings indicate that the CXCL12α‐CXCR4 axis plays an important role in the regeneration of the neuromuscular junction after motor axon injury. The present results have important implications in the effort to find therapeutics and protocols to improve recovery of function after different forms of motor axon terminal damage. |
| first_indexed | 2024-03-07T16:31:32Z |
| format | Article |
| id | doaj.art-63ca5aa313ec418b84d41f90979ff79c |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2024-03-07T16:31:32Z |
| publishDate | 2017-08-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-63ca5aa313ec418b84d41f90979ff79c2024-03-03T10:18:26ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842017-08-01981000101010.15252/emmm.201607257CXCL12α/SDF‐1 from perisynaptic Schwann cells promotes regeneration of injured motor axon terminalsSamuele Negro0Francesca Lessi1Elisa Duregotti2Paolo Aretini3Marco La Ferla4Sara Franceschi5Michele Menicagli6Elisanna Bergamin7Egle Radice8Marcus Thelen9Aram Megighian10Marco Pirazzini11Chiara M Mazzanti12Michela Rigoni13Cesare Montecucco14Department of Biomedical Sciences University of Padua Padua ItalyLaboratory of Genomics Pisa Science Foundation Pisa ItalyDepartment of Biomedical Sciences University of Padua Padua ItalyLaboratory of Genomics Pisa Science Foundation Pisa ItalyLaboratory of Genomics Pisa Science Foundation Pisa ItalyLaboratory of Genomics Pisa Science Foundation Pisa ItalyLaboratory of Genomics Pisa Science Foundation Pisa ItalyDepartment of Biomedical Sciences University of Padua Padua ItalyInstitute for Research in Biomedicine Università della Svizzera Italiana Bellinzona SwitzerlandInstitute for Research in Biomedicine Università della Svizzera Italiana Bellinzona SwitzerlandDepartment of Biomedical Sciences University of Padua Padua ItalyDepartment of Biomedical Sciences University of Padua Padua ItalyLaboratory of Genomics Pisa Science Foundation Pisa ItalyDepartment of Biomedical Sciences University of Padua Padua ItalyDepartment of Biomedical Sciences University of Padua Padua ItalyAbstract The neuromuscular junction has retained through evolution the capacity to regenerate after damage, but little is known on the inter‐cellular signals involved in its functional recovery from trauma, autoimmune attacks, or neurotoxins. We report here that CXCL12α, also abbreviated as stromal‐derived factor‐1 (SDF‐1), is produced specifically by perisynaptic Schwann cells following motor axon terminal degeneration induced by α‐latrotoxin. CXCL12α acts via binding to the neuronal CXCR4 receptor. A CXCL12α‐neutralizing antibody or a specific CXCR4 inhibitor strongly delays recovery from motor neuron degeneration in vivo. Recombinant CXCL12α in vivo accelerates neurotransmission rescue upon damage and very effectively stimulates the axon growth of spinal cord motor neurons in vitro. These findings indicate that the CXCL12α‐CXCR4 axis plays an important role in the regeneration of the neuromuscular junction after motor axon injury. The present results have important implications in the effort to find therapeutics and protocols to improve recovery of function after different forms of motor axon terminal damage.https://doi.org/10.15252/emmm.201607257CXCL12CXCR4neuromuscular junctionneuroregenerationperisynaptic Schwann cells |
| spellingShingle | Samuele Negro Francesca Lessi Elisa Duregotti Paolo Aretini Marco La Ferla Sara Franceschi Michele Menicagli Elisanna Bergamin Egle Radice Marcus Thelen Aram Megighian Marco Pirazzini Chiara M Mazzanti Michela Rigoni Cesare Montecucco CXCL12α/SDF‐1 from perisynaptic Schwann cells promotes regeneration of injured motor axon terminals EMBO Molecular Medicine CXCL12 CXCR4 neuromuscular junction neuroregeneration perisynaptic Schwann cells |
| title | CXCL12α/SDF‐1 from perisynaptic Schwann cells promotes regeneration of injured motor axon terminals |
| title_full | CXCL12α/SDF‐1 from perisynaptic Schwann cells promotes regeneration of injured motor axon terminals |
| title_fullStr | CXCL12α/SDF‐1 from perisynaptic Schwann cells promotes regeneration of injured motor axon terminals |
| title_full_unstemmed | CXCL12α/SDF‐1 from perisynaptic Schwann cells promotes regeneration of injured motor axon terminals |
| title_short | CXCL12α/SDF‐1 from perisynaptic Schwann cells promotes regeneration of injured motor axon terminals |
| title_sort | cxcl12α sdf 1 from perisynaptic schwann cells promotes regeneration of injured motor axon terminals |
| topic | CXCL12 CXCR4 neuromuscular junction neuroregeneration perisynaptic Schwann cells |
| url | https://doi.org/10.15252/emmm.201607257 |
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