Exosome-based targeted delivery of NF-κB ameliorates age-related neuroinflammation in the aged mouse brain
Abstract Neuroinflammation, a significant contributor to various neurodegenerative diseases, is strongly associated with the aging process; however, to date, no efficacious treatments for neuroinflammation have been developed. In aged mouse brains, the number of infiltrating immune cells increases,...
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Nature Publishing Group
2025-01-01
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| Series: | Experimental and Molecular Medicine |
| Online Access: | https://doi.org/10.1038/s12276-024-01388-8 |
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| author | Chae-Jeong Lee Seung Hyun Jang Jiwoo Lim Hyunju Park So-Hee Ahn Seon Young Park Hyangmi Seo Soo-Jin Song Jung-A Shin Chulhee Choi Heon Yung Gee Youn-Hee Choi |
| author_facet | Chae-Jeong Lee Seung Hyun Jang Jiwoo Lim Hyunju Park So-Hee Ahn Seon Young Park Hyangmi Seo Soo-Jin Song Jung-A Shin Chulhee Choi Heon Yung Gee Youn-Hee Choi |
| author_sort | Chae-Jeong Lee |
| collection | DOAJ |
| description | Abstract Neuroinflammation, a significant contributor to various neurodegenerative diseases, is strongly associated with the aging process; however, to date, no efficacious treatments for neuroinflammation have been developed. In aged mouse brains, the number of infiltrating immune cells increases, and the key transcription factor associated with increased chemokine levels is nuclear factor kappa B (NF-κB). Exosomes are potent therapeutics or drug delivery vehicles for various materials, including proteins and regulatory genes, to target cells. In the present study, we evaluated the therapeutic efficacy of exosomes loaded with a nondegradable form of IκB (Exo-srIκB), which inhibits the nuclear translocation of NF-κB to suppress age-related neuroinflammation. Single-cell RNA sequencing revealed that these anti-inflammatory exosomes targeted macrophages and microglia, reducing the expression of inflammation-related genes. Treatment with Exo-srIκB also suppressed the interactions between macrophages/microglia and T and B cells in the aged brain. We demonstrated that Exo-srIκB successfully alleviates neuroinflammation by primarily targeting activated macrophages and partially modulating the functions of age-related interferon-responsive microglia in the brain. Thus, our findings highlight Exo-srIκB as a potential therapeutic agent for treating age-related neuroinflammation. |
| format | Article |
| id | doaj-art-68b71e8b0bcd4c9eab7aa46d0db5e684 |
| institution | Kabale University |
| issn | 2092-6413 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Experimental and Molecular Medicine |
| spelling | doaj-art-68b71e8b0bcd4c9eab7aa46d0db5e6842025-02-09T12:14:23ZengNature Publishing GroupExperimental and Molecular Medicine2092-64132025-01-0157123524810.1038/s12276-024-01388-8Exosome-based targeted delivery of NF-κB ameliorates age-related neuroinflammation in the aged mouse brainChae-Jeong Lee0Seung Hyun Jang1Jiwoo Lim2Hyunju Park3So-Hee Ahn4Seon Young Park5Hyangmi Seo6Soo-Jin Song7Jung-A Shin8Chulhee Choi9Heon Yung Gee10Youn-Hee Choi11Department of Physiology, Inflammation-Cancer Microenvironment Research Center, Ewha Womans University College of MedicineDepartment of Pharmacology, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of MedicineDepartment of Physiology, Inflammation-Cancer Microenvironment Research Center, Ewha Womans University College of MedicineDepartment of Physiology, Inflammation-Cancer Microenvironment Research Center, Ewha Womans University College of MedicineILIAS Biologics Inc.ILIAS Biologics Inc.ILIAS Biologics Inc.Department of Anatomy, Ewha Womans University College of MedicineDepartment of Anatomy, Ewha Womans University College of MedicineILIAS Biologics Inc.Department of Pharmacology, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of MedicineDepartment of Physiology, Inflammation-Cancer Microenvironment Research Center, Ewha Womans University College of MedicineAbstract Neuroinflammation, a significant contributor to various neurodegenerative diseases, is strongly associated with the aging process; however, to date, no efficacious treatments for neuroinflammation have been developed. In aged mouse brains, the number of infiltrating immune cells increases, and the key transcription factor associated with increased chemokine levels is nuclear factor kappa B (NF-κB). Exosomes are potent therapeutics or drug delivery vehicles for various materials, including proteins and regulatory genes, to target cells. In the present study, we evaluated the therapeutic efficacy of exosomes loaded with a nondegradable form of IκB (Exo-srIκB), which inhibits the nuclear translocation of NF-κB to suppress age-related neuroinflammation. Single-cell RNA sequencing revealed that these anti-inflammatory exosomes targeted macrophages and microglia, reducing the expression of inflammation-related genes. Treatment with Exo-srIκB also suppressed the interactions between macrophages/microglia and T and B cells in the aged brain. We demonstrated that Exo-srIκB successfully alleviates neuroinflammation by primarily targeting activated macrophages and partially modulating the functions of age-related interferon-responsive microglia in the brain. Thus, our findings highlight Exo-srIκB as a potential therapeutic agent for treating age-related neuroinflammation.https://doi.org/10.1038/s12276-024-01388-8 |
| spellingShingle | Chae-Jeong Lee Seung Hyun Jang Jiwoo Lim Hyunju Park So-Hee Ahn Seon Young Park Hyangmi Seo Soo-Jin Song Jung-A Shin Chulhee Choi Heon Yung Gee Youn-Hee Choi Exosome-based targeted delivery of NF-κB ameliorates age-related neuroinflammation in the aged mouse brain Experimental and Molecular Medicine |
| title | Exosome-based targeted delivery of NF-κB ameliorates age-related neuroinflammation in the aged mouse brain |
| title_full | Exosome-based targeted delivery of NF-κB ameliorates age-related neuroinflammation in the aged mouse brain |
| title_fullStr | Exosome-based targeted delivery of NF-κB ameliorates age-related neuroinflammation in the aged mouse brain |
| title_full_unstemmed | Exosome-based targeted delivery of NF-κB ameliorates age-related neuroinflammation in the aged mouse brain |
| title_short | Exosome-based targeted delivery of NF-κB ameliorates age-related neuroinflammation in the aged mouse brain |
| title_sort | exosome based targeted delivery of nf κb ameliorates age related neuroinflammation in the aged mouse brain |
| url | https://doi.org/10.1038/s12276-024-01388-8 |
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