Activation of SIRT3 / PRDX5 signaling inhibits apoptosis after acute spinal cord injury in mice
Spinal cord injury (SCI), a traumatic condition affecting the nervous system, constitutes an orthopedic emergency that is closely associated with a significantly elevated disability rate. Excessive apoptosis not only hinders neuronal repair, but also exacerbates the deterioration of the local microe...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-10-01
|
| Series: | Brain Research Bulletin |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923025003223 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849339565299466240 |
|---|---|
| author | Hui Ni Weiping Sha Tianli Xu Qiancheng Zhu Qun Huang Jin Wang Qi Gu Yi Zhu Liming Wang Shoujin Tian Rong Gao Jianfei Ge Xiaolong Lin |
| author_facet | Hui Ni Weiping Sha Tianli Xu Qiancheng Zhu Qun Huang Jin Wang Qi Gu Yi Zhu Liming Wang Shoujin Tian Rong Gao Jianfei Ge Xiaolong Lin |
| author_sort | Hui Ni |
| collection | DOAJ |
| description | Spinal cord injury (SCI), a traumatic condition affecting the nervous system, constitutes an orthopedic emergency that is closely associated with a significantly elevated disability rate. Excessive apoptosis not only hinders neuronal repair, but also exacerbates the deterioration of the local microenvironment, thereby impeding the treatment of SCI. The present study comprehensively investigated the dynamic expression of mitochondrial deacetylase sirtuin 3 (SIRT3) in a murine model of SCI. Activation of SIRT3 with the natural agonist honokiol (HKL) facilitated neurological functional recovery by mitigating neuronal apoptosis and oxidative stress injury in vivo. Mechanistically, through comparative analysis of transcriptome alterations after global deletion of SIRT3 (Sirt3-/-), mitochondrion localized protein peroxidase peroxiredoxin 5 (PRDX5) was identified as the direct downstream effector of SIRT3. Spatially, SIRT3 and PRDX5 were colocalized within neurons in the anterior horn of the spinal cord. Genetic silencing of PRDX5 partially attenuated the protective effects of SIRT3 against neuronal apoptosis and the promotion of functional recovery. Overall, this study is the first to reveal the pivotal role of the SIRT3PRDX5 axis in modulating neuronal apoptosis after SCI, and thus offers a novel perspective on the restoration of function after SCI. |
| format | Article |
| id | doaj-art-6e132c0cd5bc4e9d8e36f734c5e7f86c |
| institution | Kabale University |
| issn | 1873-2747 |
| language | English |
| publishDate | 2025-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Research Bulletin |
| spelling | doaj-art-6e132c0cd5bc4e9d8e36f734c5e7f86c2025-08-20T03:44:06ZengElsevierBrain Research Bulletin1873-27472025-10-0123011151010.1016/j.brainresbull.2025.111510Activation of SIRT3 / PRDX5 signaling inhibits apoptosis after acute spinal cord injury in miceHui Ni0Weiping Sha1Tianli Xu2Qiancheng Zhu3Qun Huang4Jin Wang5Qi Gu6Yi Zhu7Liming Wang8Shoujin Tian9Rong Gao10Jianfei Ge11Xiaolong Lin12Department of Orthopaedic Surgery, Zhangjiagang Hospital affiliated to Soochow University, Suzhou, Jiangsu 215600, ChinaDepartment of Orthopaedic Surgery, Zhangjiagang Hospital affiliated to Soochow University, Suzhou, Jiangsu 215600, ChinaDepartment of Orthopaedic Surgery, Zhangjiagang Hospital affiliated to Soochow University, Suzhou, Jiangsu 215600, ChinaDepartment of Orthopaedic Surgery, Zhangjiagang Hospital affiliated to Soochow University, Suzhou, Jiangsu 215600, ChinaDepartment of Orthopaedic Surgery, Zhangjiagang Hospital affiliated to Soochow University, Suzhou, Jiangsu 215600, ChinaDepartment of Orthopaedic Surgery, Zhangjiagang Hospital affiliated to Soochow University, Suzhou, Jiangsu 215600, ChinaDepartment of Orthopaedic Surgery, Zhangjiagang Hospital affiliated to Soochow University, Suzhou, Jiangsu 215600, ChinaDepartment of Orthopaedic Surgery, Zhangjiagang Hospital affiliated to Soochow University, Suzhou, Jiangsu 215600, ChinaDepartment of Orthopaedic Surgery, Zhangjiagang Hospital affiliated to Soochow University, Suzhou, Jiangsu 215600, ChinaDepartment of Orthopaedic Surgery, Zhangjiagang Hospital affiliated to Soochow University, Suzhou, Jiangsu 215600, ChinaDepartment of Neurosurgery, Zhangjiagang Hospital affiliated to Soochow University, Suzhou, Jiangsu 215600, ChinaDepartment of Orthopaedic Surgery, Zhangjiagang Hospital affiliated to Soochow University, Suzhou, Jiangsu 215600, China; Correspondence to: Department of Orthopaedic Surgery, Zhangjiagang Hospital affiliated to Soochow University, No.68 West Jiyang Road, Suzhou 215600, China.Department of Orthopaedic Surgery, Zhangjiagang Hospital affiliated to Soochow University, Suzhou, Jiangsu 215600, China; Correspondence to: Department of Orthopaedic Surgery, Zhangjiagang Hospital affiliated to Soochow University, No.68 West Jiyang Road, Suzhou 215600, China.Spinal cord injury (SCI), a traumatic condition affecting the nervous system, constitutes an orthopedic emergency that is closely associated with a significantly elevated disability rate. Excessive apoptosis not only hinders neuronal repair, but also exacerbates the deterioration of the local microenvironment, thereby impeding the treatment of SCI. The present study comprehensively investigated the dynamic expression of mitochondrial deacetylase sirtuin 3 (SIRT3) in a murine model of SCI. Activation of SIRT3 with the natural agonist honokiol (HKL) facilitated neurological functional recovery by mitigating neuronal apoptosis and oxidative stress injury in vivo. Mechanistically, through comparative analysis of transcriptome alterations after global deletion of SIRT3 (Sirt3-/-), mitochondrion localized protein peroxidase peroxiredoxin 5 (PRDX5) was identified as the direct downstream effector of SIRT3. Spatially, SIRT3 and PRDX5 were colocalized within neurons in the anterior horn of the spinal cord. Genetic silencing of PRDX5 partially attenuated the protective effects of SIRT3 against neuronal apoptosis and the promotion of functional recovery. Overall, this study is the first to reveal the pivotal role of the SIRT3PRDX5 axis in modulating neuronal apoptosis after SCI, and thus offers a novel perspective on the restoration of function after SCI.http://www.sciencedirect.com/science/article/pii/S0361923025003223SIRT3PRDX5Spinal cord injuryNeuroprotectionApoptosis |
| spellingShingle | Hui Ni Weiping Sha Tianli Xu Qiancheng Zhu Qun Huang Jin Wang Qi Gu Yi Zhu Liming Wang Shoujin Tian Rong Gao Jianfei Ge Xiaolong Lin Activation of SIRT3 / PRDX5 signaling inhibits apoptosis after acute spinal cord injury in mice Brain Research Bulletin SIRT3 PRDX5 Spinal cord injury Neuroprotection Apoptosis |
| title | Activation of SIRT3 / PRDX5 signaling inhibits apoptosis after acute spinal cord injury in mice |
| title_full | Activation of SIRT3 / PRDX5 signaling inhibits apoptosis after acute spinal cord injury in mice |
| title_fullStr | Activation of SIRT3 / PRDX5 signaling inhibits apoptosis after acute spinal cord injury in mice |
| title_full_unstemmed | Activation of SIRT3 / PRDX5 signaling inhibits apoptosis after acute spinal cord injury in mice |
| title_short | Activation of SIRT3 / PRDX5 signaling inhibits apoptosis after acute spinal cord injury in mice |
| title_sort | activation of sirt3 prdx5 signaling inhibits apoptosis after acute spinal cord injury in mice |
| topic | SIRT3 PRDX5 Spinal cord injury Neuroprotection Apoptosis |
| url | http://www.sciencedirect.com/science/article/pii/S0361923025003223 |
| work_keys_str_mv | AT huini activationofsirt3prdx5signalinginhibitsapoptosisafteracutespinalcordinjuryinmice AT weipingsha activationofsirt3prdx5signalinginhibitsapoptosisafteracutespinalcordinjuryinmice AT tianlixu activationofsirt3prdx5signalinginhibitsapoptosisafteracutespinalcordinjuryinmice AT qianchengzhu activationofsirt3prdx5signalinginhibitsapoptosisafteracutespinalcordinjuryinmice AT qunhuang activationofsirt3prdx5signalinginhibitsapoptosisafteracutespinalcordinjuryinmice AT jinwang activationofsirt3prdx5signalinginhibitsapoptosisafteracutespinalcordinjuryinmice AT qigu activationofsirt3prdx5signalinginhibitsapoptosisafteracutespinalcordinjuryinmice AT yizhu activationofsirt3prdx5signalinginhibitsapoptosisafteracutespinalcordinjuryinmice AT limingwang activationofsirt3prdx5signalinginhibitsapoptosisafteracutespinalcordinjuryinmice AT shoujintian activationofsirt3prdx5signalinginhibitsapoptosisafteracutespinalcordinjuryinmice AT ronggao activationofsirt3prdx5signalinginhibitsapoptosisafteracutespinalcordinjuryinmice AT jianfeige activationofsirt3prdx5signalinginhibitsapoptosisafteracutespinalcordinjuryinmice AT xiaolonglin activationofsirt3prdx5signalinginhibitsapoptosisafteracutespinalcordinjuryinmice |