Activation of SIRT3 / PRDX5 signaling inhibits apoptosis after acute spinal cord injury in mice

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...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2025-10-01
Series:Brain Research Bulletin
Subjects:
SIRT3
PRDX5
Spinal cord injury
Neuroprotection
Apoptosis
Online Access:http://www.sciencedirect.com/science/article/pii/S0361923025003223
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Summary: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 SIRT3PRDX5 axis in modulating neuronal apoptosis after SCI, and thus offers a novel perspective on the restoration of function after SCI.
ISSN:1873-2747

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