Irisin regulates oxidative stress and mitochondrial dysfunction through the UCP2-AMPK pathway in prion diseases
Abstract Prion diseases are a group of fatal neurodegenerative disorders characterized by the abnormal folding of cellular prion proteins into pathogenic forms. The development of these diseases is intricately linked to oxidative stress and mitochondrial dysfunction. Irisin, an endogenous myokine, h...
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| Format: | Article |
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Nature Publishing Group
2025-02-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07390-w |
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| author | Pei Wen Zhixin Sun Dongming Yang Jie Li Zhiping Li Mengyang Zhao DongDong Wang Fengting Gou Jingjing Wang Yuexin Dai Deming Zhao Lifeng Yang |
| author_facet | Pei Wen Zhixin Sun Dongming Yang Jie Li Zhiping Li Mengyang Zhao DongDong Wang Fengting Gou Jingjing Wang Yuexin Dai Deming Zhao Lifeng Yang |
| author_sort | Pei Wen |
| collection | DOAJ |
| description | Abstract Prion diseases are a group of fatal neurodegenerative disorders characterized by the abnormal folding of cellular prion proteins into pathogenic forms. The development of these diseases is intricately linked to oxidative stress and mitochondrial dysfunction. Irisin, an endogenous myokine, has demonstrated considerable neuroprotective potential due to its antioxidative properties. However, the protective effects of irisin against prion diseases have yet to be clarified. Our findings indicate that treatment with exogenous irisin can mitigate the apoptosis induced by PrP106–126. Additionally, irisin significantly reduces oxidative stress and alleviates the mitochondrial dysfunction triggered by PrP106–126. Furthermore, irisin treatment targets uncoupling protein 2 (UCP2) and activates the AMPK-Nrf2 pathway, substantially improving oxidative stress and mitochondrial dysfunction in N2a cells induced by PrP106–126. These results suggest that irisin represents a novel and promising therapeutic approach for treating prion diseases. |
| format | Article |
| id | doaj-art-4274e79fdc7241cdbe54ce784d96df2b |
| institution | Kabale University |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-4274e79fdc7241cdbe54ce784d96df2b2025-02-09T12:56:42ZengNature Publishing GroupCell Death and Disease2041-48892025-02-0116111410.1038/s41419-025-07390-wIrisin regulates oxidative stress and mitochondrial dysfunction through the UCP2-AMPK pathway in prion diseasesPei Wen0Zhixin Sun1Dongming Yang2Jie Li3Zhiping Li4Mengyang Zhao5DongDong Wang6Fengting Gou7Jingjing Wang8Yuexin Dai9Deming Zhao10Lifeng Yang11National Key Laboratory of Veterinary Public Health and Safety, Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural UniversityNational Key Laboratory of Veterinary Public Health and Safety, Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural UniversityNational Key Laboratory of Veterinary Public Health and Safety, Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural UniversityNational Key Laboratory of Veterinary Public Health and Safety, Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural UniversityNational Key Laboratory of Veterinary Public Health and Safety, Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural UniversityNational Key Laboratory of Veterinary Public Health and Safety, Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural UniversityNational Key Laboratory of Veterinary Public Health and Safety, Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural UniversityNational Key Laboratory of Veterinary Public Health and Safety, Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural UniversityNational Key Laboratory of Veterinary Public Health and Safety, Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural UniversityNational Key Laboratory of Veterinary Public Health and Safety, Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural UniversityNational Key Laboratory of Veterinary Public Health and Safety, Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural UniversityNational Key Laboratory of Veterinary Public Health and Safety, Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural UniversityAbstract Prion diseases are a group of fatal neurodegenerative disorders characterized by the abnormal folding of cellular prion proteins into pathogenic forms. The development of these diseases is intricately linked to oxidative stress and mitochondrial dysfunction. Irisin, an endogenous myokine, has demonstrated considerable neuroprotective potential due to its antioxidative properties. However, the protective effects of irisin against prion diseases have yet to be clarified. Our findings indicate that treatment with exogenous irisin can mitigate the apoptosis induced by PrP106–126. Additionally, irisin significantly reduces oxidative stress and alleviates the mitochondrial dysfunction triggered by PrP106–126. Furthermore, irisin treatment targets uncoupling protein 2 (UCP2) and activates the AMPK-Nrf2 pathway, substantially improving oxidative stress and mitochondrial dysfunction in N2a cells induced by PrP106–126. These results suggest that irisin represents a novel and promising therapeutic approach for treating prion diseases.https://doi.org/10.1038/s41419-025-07390-w |
| spellingShingle | Pei Wen Zhixin Sun Dongming Yang Jie Li Zhiping Li Mengyang Zhao DongDong Wang Fengting Gou Jingjing Wang Yuexin Dai Deming Zhao Lifeng Yang Irisin regulates oxidative stress and mitochondrial dysfunction through the UCP2-AMPK pathway in prion diseases Cell Death and Disease |
| title | Irisin regulates oxidative stress and mitochondrial dysfunction through the UCP2-AMPK pathway in prion diseases |
| title_full | Irisin regulates oxidative stress and mitochondrial dysfunction through the UCP2-AMPK pathway in prion diseases |
| title_fullStr | Irisin regulates oxidative stress and mitochondrial dysfunction through the UCP2-AMPK pathway in prion diseases |
| title_full_unstemmed | Irisin regulates oxidative stress and mitochondrial dysfunction through the UCP2-AMPK pathway in prion diseases |
| title_short | Irisin regulates oxidative stress and mitochondrial dysfunction through the UCP2-AMPK pathway in prion diseases |
| title_sort | irisin regulates oxidative stress and mitochondrial dysfunction through the ucp2 ampk pathway in prion diseases |
| url | https://doi.org/10.1038/s41419-025-07390-w |
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