Oligodendrocytes drive neuroinflammation and neurodegeneration in Parkinson’s disease via the prosaposin-GPR37-IL-6 axis
Summary: Parkinson’s disease (PD) is a common neurodegenerative disease and is difficult to treat due to its elusive mechanisms. Recent studies have identified a striking association between oligodendrocytes and PD progression, yet how oligodendrocytes regulate the pathogenesis of PD is still unknow...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-02-01
|
| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725000373 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832087712820101120 |
|---|---|
| author | Qiang Ma Jin-Lan Tian Yao Lou Ran Guo Xiao-Ru Ma Jian-Bin Wu Jing Yang Bing-Jie Tang Shun Li Mengsheng Qiu Shumin Duan Jing-Wei Zhao Jing Zhang Zhen-Zhong Xu |
| author_facet | Qiang Ma Jin-Lan Tian Yao Lou Ran Guo Xiao-Ru Ma Jian-Bin Wu Jing Yang Bing-Jie Tang Shun Li Mengsheng Qiu Shumin Duan Jing-Wei Zhao Jing Zhang Zhen-Zhong Xu |
| author_sort | Qiang Ma |
| collection | DOAJ |
| description | Summary: Parkinson’s disease (PD) is a common neurodegenerative disease and is difficult to treat due to its elusive mechanisms. Recent studies have identified a striking association between oligodendrocytes and PD progression, yet how oligodendrocytes regulate the pathogenesis of PD is still unknown. Here, we show that G-protein-coupled receptor 37 (GPR37) is upregulated in oligodendrocytes of the substantia nigra and that prosaposin (PSAP) secretion is increased in parkinsonian mice. The released PSAP can induce interleukin (IL)-6 upregulation and secretion from oligodendrocytes via a GPR37-dependent pathway, resulting in enhanced neuroinflammation, dopamine neuron degeneration, and behavioral deficits. GPR37 deficiency in oligodendrocytes prevents neurodegeneration in multiple PD models. Finally, the hallmarks of the PSAP-GPR37-IL-6 axis are observed in patients with PD. Thus, our results reveal that dopaminergic neurons interact with oligodendrocytes via secreted PSAP, and our findings identify the PSAP-GPR37-IL-6 axis as a driver of PD pathogenesis and a potential therapeutic target that might alleviate PD progression in patients. |
| format | Article |
| id | doaj-art-47c249a378a24a1dafdbeab097596241 |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-47c249a378a24a1dafdbeab0975962412025-02-06T05:11:31ZengElsevierCell Reports2211-12472025-02-01442115266Oligodendrocytes drive neuroinflammation and neurodegeneration in Parkinson’s disease via the prosaposin-GPR37-IL-6 axisQiang Ma0Jin-Lan Tian1Yao Lou2Ran Guo3Xiao-Ru Ma4Jian-Bin Wu5Jing Yang6Bing-Jie Tang7Shun Li8Mengsheng Qiu9Shumin Duan10Jing-Wei Zhao11Jing Zhang12Zhen-Zhong Xu13Department of Anesthesiology of First Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou 310058, China; Center for Rehabilitation Medicine, Department of Anesthesiology and Department of Pain Management, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou 310014, China; Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, Zhejiang University, Hangzhou 311121, China; Corresponding authorDepartment of Anesthesiology of First Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou 310058, China; Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, Zhejiang University, Hangzhou 311121, China; Nanhu Brain–Computer Interface Institute, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou 311100, ChinaCenter for Rehabilitation Medicine, Department of Anesthesiology and Department of Pain Management, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou 310014, ChinaCenter for Rehabilitation Medicine, Department of Anesthesiology and Department of Pain Management, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou 310014, China; Corresponding authorDepartment of Pathology of Sir Run Run Shaw Hospital and Department of Human Anatomy, Histology and Embryology, System Medicine Research Center, Zhejiang University School of Medicine, Hangzhou 310058, ChinaDepartment of Pathology of Sir Run Run Shaw Hospital and Department of Human Anatomy, Histology and Embryology, System Medicine Research Center, Zhejiang University School of Medicine, Hangzhou 310058, ChinaDepartment of Anesthesiology of First Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou 310058, China; Center for Rehabilitation Medicine, Department of Anesthesiology and Department of Pain Management, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou 310014, ChinaDepartment of Anesthesiology of First Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou 310058, China; Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, Zhejiang University, Hangzhou 311121, China; Nanhu Brain–Computer Interface Institute, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou 311100, ChinaCenter for Rehabilitation Medicine, Department of Anesthesiology and Department of Pain Management, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou 310014, ChinaZhejiang Key Laboratory of Organ Development and Regeneration, Institute of Life Sciences, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 311121, ChinaDepartment of Anesthesiology of First Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou 310058, China; Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, Zhejiang University, Hangzhou 311121, China; Nanhu Brain–Computer Interface Institute, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou 311100, ChinaDepartment of Pathology of Sir Run Run Shaw Hospital and Department of Human Anatomy, Histology and Embryology, System Medicine Research Center, Zhejiang University School of Medicine, Hangzhou 310058, ChinaDepartment of Anesthesiology of First Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou 310058, China; Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, Zhejiang University, Hangzhou 311121, China; Department of Pathology of First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310002, China; National Health and Disease Human Brain Tissue Resource Center, Zhejiang University, Hangzhou 310002, ChinaDepartment of Anesthesiology of First Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou 310058, China; Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, Zhejiang University, Hangzhou 311121, China; Nanhu Brain–Computer Interface Institute, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou 311100, China; Corresponding authorSummary: Parkinson’s disease (PD) is a common neurodegenerative disease and is difficult to treat due to its elusive mechanisms. Recent studies have identified a striking association between oligodendrocytes and PD progression, yet how oligodendrocytes regulate the pathogenesis of PD is still unknown. Here, we show that G-protein-coupled receptor 37 (GPR37) is upregulated in oligodendrocytes of the substantia nigra and that prosaposin (PSAP) secretion is increased in parkinsonian mice. The released PSAP can induce interleukin (IL)-6 upregulation and secretion from oligodendrocytes via a GPR37-dependent pathway, resulting in enhanced neuroinflammation, dopamine neuron degeneration, and behavioral deficits. GPR37 deficiency in oligodendrocytes prevents neurodegeneration in multiple PD models. Finally, the hallmarks of the PSAP-GPR37-IL-6 axis are observed in patients with PD. Thus, our results reveal that dopaminergic neurons interact with oligodendrocytes via secreted PSAP, and our findings identify the PSAP-GPR37-IL-6 axis as a driver of PD pathogenesis and a potential therapeutic target that might alleviate PD progression in patients.http://www.sciencedirect.com/science/article/pii/S2211124725000373CP: Neuroscience |
| spellingShingle | Qiang Ma Jin-Lan Tian Yao Lou Ran Guo Xiao-Ru Ma Jian-Bin Wu Jing Yang Bing-Jie Tang Shun Li Mengsheng Qiu Shumin Duan Jing-Wei Zhao Jing Zhang Zhen-Zhong Xu Oligodendrocytes drive neuroinflammation and neurodegeneration in Parkinson’s disease via the prosaposin-GPR37-IL-6 axis Cell Reports CP: Neuroscience |
| title | Oligodendrocytes drive neuroinflammation and neurodegeneration in Parkinson’s disease via the prosaposin-GPR37-IL-6 axis |
| title_full | Oligodendrocytes drive neuroinflammation and neurodegeneration in Parkinson’s disease via the prosaposin-GPR37-IL-6 axis |
| title_fullStr | Oligodendrocytes drive neuroinflammation and neurodegeneration in Parkinson’s disease via the prosaposin-GPR37-IL-6 axis |
| title_full_unstemmed | Oligodendrocytes drive neuroinflammation and neurodegeneration in Parkinson’s disease via the prosaposin-GPR37-IL-6 axis |
| title_short | Oligodendrocytes drive neuroinflammation and neurodegeneration in Parkinson’s disease via the prosaposin-GPR37-IL-6 axis |
| title_sort | oligodendrocytes drive neuroinflammation and neurodegeneration in parkinson s disease via the prosaposin gpr37 il 6 axis |
| topic | CP: Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725000373 |
| work_keys_str_mv | AT qiangma oligodendrocytesdriveneuroinflammationandneurodegenerationinparkinsonsdiseaseviatheprosaposingpr37il6axis AT jinlantian oligodendrocytesdriveneuroinflammationandneurodegenerationinparkinsonsdiseaseviatheprosaposingpr37il6axis AT yaolou oligodendrocytesdriveneuroinflammationandneurodegenerationinparkinsonsdiseaseviatheprosaposingpr37il6axis AT ranguo oligodendrocytesdriveneuroinflammationandneurodegenerationinparkinsonsdiseaseviatheprosaposingpr37il6axis AT xiaoruma oligodendrocytesdriveneuroinflammationandneurodegenerationinparkinsonsdiseaseviatheprosaposingpr37il6axis AT jianbinwu oligodendrocytesdriveneuroinflammationandneurodegenerationinparkinsonsdiseaseviatheprosaposingpr37il6axis AT jingyang oligodendrocytesdriveneuroinflammationandneurodegenerationinparkinsonsdiseaseviatheprosaposingpr37il6axis AT bingjietang oligodendrocytesdriveneuroinflammationandneurodegenerationinparkinsonsdiseaseviatheprosaposingpr37il6axis AT shunli oligodendrocytesdriveneuroinflammationandneurodegenerationinparkinsonsdiseaseviatheprosaposingpr37il6axis AT mengshengqiu oligodendrocytesdriveneuroinflammationandneurodegenerationinparkinsonsdiseaseviatheprosaposingpr37il6axis AT shuminduan oligodendrocytesdriveneuroinflammationandneurodegenerationinparkinsonsdiseaseviatheprosaposingpr37il6axis AT jingweizhao oligodendrocytesdriveneuroinflammationandneurodegenerationinparkinsonsdiseaseviatheprosaposingpr37il6axis AT jingzhang oligodendrocytesdriveneuroinflammationandneurodegenerationinparkinsonsdiseaseviatheprosaposingpr37il6axis AT zhenzhongxu oligodendrocytesdriveneuroinflammationandneurodegenerationinparkinsonsdiseaseviatheprosaposingpr37il6axis |