Athlete-derived extracellular vesicles protect against spinal cord injury via inhibition of neuronal ferroptosis
Spinal cord injury (SCI) causes high morbidity, disability, and mortality, while current surgical and pharmacological treatments provide limited benefit. Ferroptosis, a newly recognized form of regulated cell death, contributes critically to SCI pathology, and targeting this process may enhance neuronal survival. Extracellular vesicles, key mediators of intercellular communication, are emerging as promising therapeutic agents for central nervous system injury. Here, we examined the role of athlete-derived plasma extracellular vesicles (AEVs) in neuronal ferroptosis and motor function recovery after SCI. In a murine model, AEVs markedly inhibited ferroptosis and improved motor outcomes. Mechanistically, AEVs delivered RNF216, which promoted ubiquitination and degradation of NOX1, thereby reducing ferroptotic damage and facilitating recovery. Moreover, RNF216-enriched vesicles enhanced synaptic plasticity, supporting neuronal regeneration and network reestablishment. These findings reveal a previously unrecognized RNF216-NOX1 axis in SCI and highlight AEVs as a previously unidentified therapeutic strategy.
Authors
- Liang Wang (ORCID: https://orcid.org/0000-0002-8868-8449)
- Xuhui Ge (ORCID: https://orcid.org/0000-0003-2881-9184)
- Chuandong Lang (ORCID: https://orcid.org/0009-0008-3831-6592)
- J.J. Wang (ORCID: https://orcid.org/0009-0007-0856-4125)
- Weihua Cai (ORCID: https://orcid.org/0000-0001-5597-234X)
- Feng Zhang (ORCID: https://orcid.org/0000-0003-2316-0392)
- Wenzhi Zhang (ORCID: https://orcid.org/0000-0003-3723-9050)
- Tao Hu (ORCID: https://orcid.org/0009-0009-5345-902X)
- Yongjin Sun (ORCID: https://orcid.org/0000-0002-0474-8556)
- Feng Hu
- Wei Liu (ORCID: https://orcid.org/0009-0001-6937-2430)
- Wenbin Xu (ORCID: https://orcid.org/0009-0004-7878-659X)
- Yuluo Rong (ORCID: https://orcid.org/0009-0005-6048-5761)
Institutions
- Shanghai University (CN)
- University of Science and Technology of China (CN)
- Army Medical University (CN)
- Second Military Medical University (CN)
- Nantong University (CN)
- Daping Hospital (CN)
- Shanghai Changzheng Hospital (CN)
- The Affiliated Taizhou People's Hospital of Nanjing Medical University (CN)
- Jiangsu Province Hospital (CN)
- Taizhou University (CN)
- Nanjing Medical University (CN)
Publication Details
- Journal
- Science Advances
- Published
- 2025-12-12
- DOI
- https://doi.org/10.1126/sciadv.adx7695
- Citations
- 1
- Primary Topic
- Extracellular vesicles in disease
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- Anhui Provincial Department of Education
- Natural Science Foundation of Anhui Province