Irisin exhibits neuroprotection by preventing mitochondrial damage in Parkinson’s disease
Abstract Exercise has been proposed as an effective non-pharmacological management for Parkinson’s disease (PD) patients. Irisin, a recently identified myokine, is increased by exercise and plays pivotal roles in energy metabolism. However, it remains unknown whether irisin has any protective effect...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-01-01
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| Series: | npj Parkinson's Disease |
| Online Access: | https://doi.org/10.1038/s41531-023-00453-9 |
| _version_ | 1797422227394658304 |
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| author | Xi Zhang Sutong Xu Yong Hu Qiulu Liu Chenming Liu Huazhen Chai Yuping Luo Lingjing Jin Siguang Li |
| author_facet | Xi Zhang Sutong Xu Yong Hu Qiulu Liu Chenming Liu Huazhen Chai Yuping Luo Lingjing Jin Siguang Li |
| author_sort | Xi Zhang |
| collection | DOAJ |
| description | Abstract Exercise has been proposed as an effective non-pharmacological management for Parkinson’s disease (PD) patients. Irisin, a recently identified myokine, is increased by exercise and plays pivotal roles in energy metabolism. However, it remains unknown whether irisin has any protective effects on PD. Here, we found that serum irisin levels of PD patients were markedly elevated after 12-week regular exercise, which had a positive correlation with improved balance function scored by Berg Balance Scale. Treatment with exogenous irisin could improve motor function, and reduce dopaminergic neurodegeneration in PD models. Meanwhile, irisin could reduce cell apoptosis by renovating mitochondrial function in PD models, which was reflected in decreased oxidative stress, increased mitochondrial complex I activity and mitochondrial content, increased mitochondrial biogenesis, and repaired mitochondrial morphology. Furthermore, irisin regulated the aforementioned aspects by upregulating downstream Akt signaling pathway and ERK1/2 signaling pathway through integrin receptors rather than directly targeting mitochondria. With the use of small-molecule inhibitors, it was found that irisin can reduce apoptosis, restore normal mitochondrial biogenesis, and improve mitochondrial morphology and dynamic balance in PD models by activating Akt signaling pathway and ERK1/2 signaling pathway. And irisin reduced oxidative stress via activating ERK1/2 signaling pathway. The results revealed that exogenous irisin conferred neuroprotection relieving apoptosis and oxidative stress, restraining mitochondrial fragmentation, and promoting mitochondrial respiration and biogenesis in PD models, and irisin exerted the aforementioned effects by activating Akt signaling pathway and ERK1/2 signaling pathway. Thus, peripherally delivered irisin might be a promising candidate for therapeutic targeting of PD. |
| first_indexed | 2024-03-09T07:29:11Z |
| format | Article |
| id | doaj.art-5ca40c6c32fa4670a302bd8c69b41326 |
| institution | Directory Open Access Journal |
| issn | 2373-8057 |
| language | English |
| last_indexed | 2024-03-09T07:29:11Z |
| publishDate | 2023-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Parkinson's Disease |
| spelling | doaj.art-5ca40c6c32fa4670a302bd8c69b413262023-12-03T06:38:17ZengNature Portfolionpj Parkinson's Disease2373-80572023-01-019111810.1038/s41531-023-00453-9Irisin exhibits neuroprotection by preventing mitochondrial damage in Parkinson’s diseaseXi Zhang0Sutong Xu1Yong Hu2Qiulu Liu3Chenming Liu4Huazhen Chai5Yuping Luo6Lingjing Jin7Siguang Li8Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopedic Department of Tongji Hospital, Tongji University School of MedicineKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopedic Department of Tongji Hospital, Tongji University School of MedicineDepartment of Neurology, Tongji Hospital, Tongji University School of MedicineKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopedic Department of Tongji Hospital, Tongji University School of MedicineKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopedic Department of Tongji Hospital, Tongji University School of MedicineKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopedic Department of Tongji Hospital, Tongji University School of MedicineKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopedic Department of Tongji Hospital, Tongji University School of MedicineDepartment of Neurology and Neurological Rehabilitation, Shanghai Yangzhi Rehabilitation Hospital, Tongji University School of MedicineKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopedic Department of Tongji Hospital, Tongji University School of MedicineAbstract Exercise has been proposed as an effective non-pharmacological management for Parkinson’s disease (PD) patients. Irisin, a recently identified myokine, is increased by exercise and plays pivotal roles in energy metabolism. However, it remains unknown whether irisin has any protective effects on PD. Here, we found that serum irisin levels of PD patients were markedly elevated after 12-week regular exercise, which had a positive correlation with improved balance function scored by Berg Balance Scale. Treatment with exogenous irisin could improve motor function, and reduce dopaminergic neurodegeneration in PD models. Meanwhile, irisin could reduce cell apoptosis by renovating mitochondrial function in PD models, which was reflected in decreased oxidative stress, increased mitochondrial complex I activity and mitochondrial content, increased mitochondrial biogenesis, and repaired mitochondrial morphology. Furthermore, irisin regulated the aforementioned aspects by upregulating downstream Akt signaling pathway and ERK1/2 signaling pathway through integrin receptors rather than directly targeting mitochondria. With the use of small-molecule inhibitors, it was found that irisin can reduce apoptosis, restore normal mitochondrial biogenesis, and improve mitochondrial morphology and dynamic balance in PD models by activating Akt signaling pathway and ERK1/2 signaling pathway. And irisin reduced oxidative stress via activating ERK1/2 signaling pathway. The results revealed that exogenous irisin conferred neuroprotection relieving apoptosis and oxidative stress, restraining mitochondrial fragmentation, and promoting mitochondrial respiration and biogenesis in PD models, and irisin exerted the aforementioned effects by activating Akt signaling pathway and ERK1/2 signaling pathway. Thus, peripherally delivered irisin might be a promising candidate for therapeutic targeting of PD.https://doi.org/10.1038/s41531-023-00453-9 |
| spellingShingle | Xi Zhang Sutong Xu Yong Hu Qiulu Liu Chenming Liu Huazhen Chai Yuping Luo Lingjing Jin Siguang Li Irisin exhibits neuroprotection by preventing mitochondrial damage in Parkinson’s disease npj Parkinson's Disease |
| title | Irisin exhibits neuroprotection by preventing mitochondrial damage in Parkinson’s disease |
| title_full | Irisin exhibits neuroprotection by preventing mitochondrial damage in Parkinson’s disease |
| title_fullStr | Irisin exhibits neuroprotection by preventing mitochondrial damage in Parkinson’s disease |
| title_full_unstemmed | Irisin exhibits neuroprotection by preventing mitochondrial damage in Parkinson’s disease |
| title_short | Irisin exhibits neuroprotection by preventing mitochondrial damage in Parkinson’s disease |
| title_sort | irisin exhibits neuroprotection by preventing mitochondrial damage in parkinson s disease |
| url | https://doi.org/10.1038/s41531-023-00453-9 |
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