Overexpression of the X-Linked Inhibitor of Apoptosis Protein (XIAP) in Neurons Improves Cell Survival and the Functional Outcome after Traumatic Spinal Cord Injury
Mechanical trauma to the spinal cord causes extensive neuronal death, contributing to the loss of sensory-motor and autonomic functions below the injury location. Apoptosis affects neurons after spinal cord injury (SCI) and is associated with increased caspase activity. Cleavage of X-linked inhibito...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/3/2791 |
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| author | David Reigada Rodrigo M. Maza Teresa Muñoz-Galdeano María Asunción Barreda-Manso Altea Soto Dan Lindholm Rosa Navarro-Ruíz Manuel Nieto-Díaz |
| author_facet | David Reigada Rodrigo M. Maza Teresa Muñoz-Galdeano María Asunción Barreda-Manso Altea Soto Dan Lindholm Rosa Navarro-Ruíz Manuel Nieto-Díaz |
| author_sort | David Reigada |
| collection | DOAJ |
| description | Mechanical trauma to the spinal cord causes extensive neuronal death, contributing to the loss of sensory-motor and autonomic functions below the injury location. Apoptosis affects neurons after spinal cord injury (SCI) and is associated with increased caspase activity. Cleavage of X-linked inhibitor of apoptosis protein (XIAP) after SCI may contribute to this rise in caspase activity. Accordingly, we have shown that the elevation of XIAP resulted in increased neuronal survival after SCI and improved functional recovery. Therefore, we hypothesise that neuronal overexpression of XIAP can be neuroprotective after SCI with improved functional recovery. In line with this, studies of a transgenic mice with overexpression of XIAP in neurons revealed that higher levels of XIAP after spinal cord trauma favours neuronal survival, tissue preservation, and motor recovery after the spinal cord trauma. Using human SH-SY5Y cells overexpressing XIAP, we further showed that XIAP reduced caspase activity and apoptotic cell death after pro-apoptotic stimuli. In conclusion, this study shows that the levels of XIAP expression are an important factor for the outcome of spinal cord trauma and identifies XIAP as an important therapeutic target for alleviating the deleterious effects of SCI. |
| first_indexed | 2024-03-11T09:39:45Z |
| format | Article |
| id | doaj.art-469f931d563b44e79d230519e4df9ca0 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:39:45Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-469f931d563b44e79d230519e4df9ca02023-11-16T17:03:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01243279110.3390/ijms24032791Overexpression of the X-Linked Inhibitor of Apoptosis Protein (XIAP) in Neurons Improves Cell Survival and the Functional Outcome after Traumatic Spinal Cord InjuryDavid Reigada0Rodrigo M. Maza1Teresa Muñoz-Galdeano2María Asunción Barreda-Manso3Altea Soto4Dan Lindholm5Rosa Navarro-Ruíz6Manuel Nieto-Díaz7Molecular Neuroprotection Group, Research Unit, National Hospital for Paraplegics (SESCAM), 45071 Toledo, SpainMolecular Neuroprotection Group, Research Unit, National Hospital for Paraplegics (SESCAM), 45071 Toledo, SpainMolecular Neuroprotection Group, Research Unit, National Hospital for Paraplegics (SESCAM), 45071 Toledo, SpainMolecular Neuroprotection Group, Research Unit, National Hospital for Paraplegics (SESCAM), 45071 Toledo, SpainMolecular Neuroprotection Group, Research Unit, National Hospital for Paraplegics (SESCAM), 45071 Toledo, SpainDepartment of Biochemistry and Developmental Biology, Faculty of Medicine, University of Helsinki, 00290 Helsinki, FinlandMolecular Neuroprotection Group, Research Unit, National Hospital for Paraplegics (SESCAM), 45071 Toledo, SpainMolecular Neuroprotection Group, Research Unit, National Hospital for Paraplegics (SESCAM), 45071 Toledo, SpainMechanical trauma to the spinal cord causes extensive neuronal death, contributing to the loss of sensory-motor and autonomic functions below the injury location. Apoptosis affects neurons after spinal cord injury (SCI) and is associated with increased caspase activity. Cleavage of X-linked inhibitor of apoptosis protein (XIAP) after SCI may contribute to this rise in caspase activity. Accordingly, we have shown that the elevation of XIAP resulted in increased neuronal survival after SCI and improved functional recovery. Therefore, we hypothesise that neuronal overexpression of XIAP can be neuroprotective after SCI with improved functional recovery. In line with this, studies of a transgenic mice with overexpression of XIAP in neurons revealed that higher levels of XIAP after spinal cord trauma favours neuronal survival, tissue preservation, and motor recovery after the spinal cord trauma. Using human SH-SY5Y cells overexpressing XIAP, we further showed that XIAP reduced caspase activity and apoptotic cell death after pro-apoptotic stimuli. In conclusion, this study shows that the levels of XIAP expression are an important factor for the outcome of spinal cord trauma and identifies XIAP as an important therapeutic target for alleviating the deleterious effects of SCI.https://www.mdpi.com/1422-0067/24/3/2791spinal cord injuryX-linked inhibitor of apoptosis proteinneuroprotectionapoptosistransgenic mice |
| spellingShingle | David Reigada Rodrigo M. Maza Teresa Muñoz-Galdeano María Asunción Barreda-Manso Altea Soto Dan Lindholm Rosa Navarro-Ruíz Manuel Nieto-Díaz Overexpression of the X-Linked Inhibitor of Apoptosis Protein (XIAP) in Neurons Improves Cell Survival and the Functional Outcome after Traumatic Spinal Cord Injury International Journal of Molecular Sciences spinal cord injury X-linked inhibitor of apoptosis protein neuroprotection apoptosis transgenic mice |
| title | Overexpression of the X-Linked Inhibitor of Apoptosis Protein (XIAP) in Neurons Improves Cell Survival and the Functional Outcome after Traumatic Spinal Cord Injury |
| title_full | Overexpression of the X-Linked Inhibitor of Apoptosis Protein (XIAP) in Neurons Improves Cell Survival and the Functional Outcome after Traumatic Spinal Cord Injury |
| title_fullStr | Overexpression of the X-Linked Inhibitor of Apoptosis Protein (XIAP) in Neurons Improves Cell Survival and the Functional Outcome after Traumatic Spinal Cord Injury |
| title_full_unstemmed | Overexpression of the X-Linked Inhibitor of Apoptosis Protein (XIAP) in Neurons Improves Cell Survival and the Functional Outcome after Traumatic Spinal Cord Injury |
| title_short | Overexpression of the X-Linked Inhibitor of Apoptosis Protein (XIAP) in Neurons Improves Cell Survival and the Functional Outcome after Traumatic Spinal Cord Injury |
| title_sort | overexpression of the x linked inhibitor of apoptosis protein xiap in neurons improves cell survival and the functional outcome after traumatic spinal cord injury |
| topic | spinal cord injury X-linked inhibitor of apoptosis protein neuroprotection apoptosis transgenic mice |
| url | https://www.mdpi.com/1422-0067/24/3/2791 |
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