CD44 deficiency represses neuroinflammation and rescues dopaminergic neurons in a mouse model of Parkinson’s disease
CD44 is a transmembrane protein that transduces extracellular stimuli to immune response. Neuroinflammation is a causative factor in neurodegenerative diseases, such as Parkinson’s disease (PD). Owing to its role in inflammation, this study investigated whether CD44 is involved in the pathological p...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-03-01
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| Series: | Pharmacological Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661822000780 |
| _version_ | 1797366641872338944 |
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| author | Yuejun Wang Li Li Yuting Wu Shouping Zhang Qianqian Ju Yinuo Yang Yan Jin Hui Shi Cheng Sun |
| author_facet | Yuejun Wang Li Li Yuting Wu Shouping Zhang Qianqian Ju Yinuo Yang Yan Jin Hui Shi Cheng Sun |
| author_sort | Yuejun Wang |
| collection | DOAJ |
| description | CD44 is a transmembrane protein that transduces extracellular stimuli to immune response. Neuroinflammation is a causative factor in neurodegenerative diseases, such as Parkinson’s disease (PD). Owing to its role in inflammation, this study investigated whether CD44 is involved in the pathological progression of PD. Our data showed that CD44 deficiency largely abolished proinflammatory cytokine expression in primary microglia and astrocytes. In PD model mice, CD44 knockout improved behavioral defects, prevented TH loss in the SNpc and striatum, and blocked activation of microglia and astrocytes. Moreover, CD44 neutralization by anti-CD44 antibody recapitulated the phenotypes observed in CD44 knockout mice. Mechanistically, CD44 neutralization blocked TLR4 expression and NF-κB p65 nuclear translocation induced by lipopolysaccharide in BV2 cells. Overall, our results indicate that CD44 deficiency has a beneficial role against PD, which is likely due to repression of the TLR4/NF-κB axis, leading to reduced neuroinflammation. Therefore, CD44 might be a therapeutic target for the development of anti-PD agents. |
| first_indexed | 2024-03-08T17:06:35Z |
| format | Article |
| id | doaj.art-2083d5bcd3f74dd8a12dce174f4e04e9 |
| institution | Directory Open Access Journal |
| issn | 1096-1186 |
| language | English |
| last_indexed | 2024-03-08T17:06:35Z |
| publishDate | 2022-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj.art-2083d5bcd3f74dd8a12dce174f4e04e92024-01-04T04:36:32ZengElsevierPharmacological Research1096-11862022-03-01177106133CD44 deficiency represses neuroinflammation and rescues dopaminergic neurons in a mouse model of Parkinson’s diseaseYuejun Wang0Li Li1Yuting Wu2Shouping Zhang3Qianqian Ju4Yinuo Yang5Yan Jin6Hui Shi7Cheng Sun8NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, 19 Qixiu Road, Nantong, China; Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, China; Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Nantong University, 19 Qixiu Road, Nantong, ChinaNMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, 19 Qixiu Road, Nantong, China; Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, China; Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Nantong University, 19 Qixiu Road, Nantong, ChinaNMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, 19 Qixiu Road, Nantong, China; Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, China; Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Nantong University, 19 Qixiu Road, Nantong, ChinaNMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, 19 Qixiu Road, Nantong, China; Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, China; Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Nantong University, 19 Qixiu Road, Nantong, ChinaDepartment of Cardiothoracic Surgery, Nantong Key Laboratory of Translational Medicine in Cardiothoracic Diseases, Nantong Clinical Medical Research Center of Cardiothoracic Diseases, and Institution of Translational Medicine in Cardiothoracic Diseases, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China; Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, ChinaNMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, 19 Qixiu Road, Nantong, China; Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, China; Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Nantong University, 19 Qixiu Road, Nantong, ChinaSchool of Life Sciences, Nantong University, Nantong, China; Corresponding authors.Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China; Corresponding authors.NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, 19 Qixiu Road, Nantong, China; Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, China; Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Nantong University, 19 Qixiu Road, Nantong, China; Department of Cardiothoracic Surgery, Nantong Key Laboratory of Translational Medicine in Cardiothoracic Diseases, Nantong Clinical Medical Research Center of Cardiothoracic Diseases, and Institution of Translational Medicine in Cardiothoracic Diseases, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China; Corresponding author at: NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, 19 Qixiu Road, Nantong, China.CD44 is a transmembrane protein that transduces extracellular stimuli to immune response. Neuroinflammation is a causative factor in neurodegenerative diseases, such as Parkinson’s disease (PD). Owing to its role in inflammation, this study investigated whether CD44 is involved in the pathological progression of PD. Our data showed that CD44 deficiency largely abolished proinflammatory cytokine expression in primary microglia and astrocytes. In PD model mice, CD44 knockout improved behavioral defects, prevented TH loss in the SNpc and striatum, and blocked activation of microglia and astrocytes. Moreover, CD44 neutralization by anti-CD44 antibody recapitulated the phenotypes observed in CD44 knockout mice. Mechanistically, CD44 neutralization blocked TLR4 expression and NF-κB p65 nuclear translocation induced by lipopolysaccharide in BV2 cells. Overall, our results indicate that CD44 deficiency has a beneficial role against PD, which is likely due to repression of the TLR4/NF-κB axis, leading to reduced neuroinflammation. Therefore, CD44 might be a therapeutic target for the development of anti-PD agents.http://www.sciencedirect.com/science/article/pii/S1043661822000780CD44NeuroinflammationGlial cellsTLR4NF-κBParkinson’s disease |
| spellingShingle | Yuejun Wang Li Li Yuting Wu Shouping Zhang Qianqian Ju Yinuo Yang Yan Jin Hui Shi Cheng Sun CD44 deficiency represses neuroinflammation and rescues dopaminergic neurons in a mouse model of Parkinson’s disease Pharmacological Research CD44 Neuroinflammation Glial cells TLR4 NF-κB Parkinson’s disease |
| title | CD44 deficiency represses neuroinflammation and rescues dopaminergic neurons in a mouse model of Parkinson’s disease |
| title_full | CD44 deficiency represses neuroinflammation and rescues dopaminergic neurons in a mouse model of Parkinson’s disease |
| title_fullStr | CD44 deficiency represses neuroinflammation and rescues dopaminergic neurons in a mouse model of Parkinson’s disease |
| title_full_unstemmed | CD44 deficiency represses neuroinflammation and rescues dopaminergic neurons in a mouse model of Parkinson’s disease |
| title_short | CD44 deficiency represses neuroinflammation and rescues dopaminergic neurons in a mouse model of Parkinson’s disease |
| title_sort | cd44 deficiency represses neuroinflammation and rescues dopaminergic neurons in a mouse model of parkinson s disease |
| topic | CD44 Neuroinflammation Glial cells TLR4 NF-κB Parkinson’s disease |
| url | http://www.sciencedirect.com/science/article/pii/S1043661822000780 |
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