Language:

Astrocyte-targeting therapy rescues cognitive impairment caused by neuroinflammation via the Nrf2 pathway

Proceedings of the National Academy of Sciences - PNAS, 2023-08, Vol.120 (33), p.e2303809120-e2303809120 [Peer Reviewed Journal]

Copyright National Academy of Sciences Aug 15, 2023 ;Copyright © 2023 the Author(s). Published by PNAS. 2023 ;ISSN: 0027-8424 ;EISSN: 1091-6490 ;DOI: 10.1073/pnas.2303809120 ;PMID: 37549281

Full text available

Citations Cited by

Actions
1. Add to My Research
2. Remove from My Research
3. E-mail
4. Print
5. Permalink
6. Citation
7. EasyBib
8. EndNote
9. RefWorks
10. Delicious
11. Export RIS
12. Export BibTeX

Title:
Astrocyte-targeting therapy rescues cognitive impairment caused by neuroinflammation via the Nrf2 pathway
Author: Nakano-Kobayashi, Akiko ; Canela, Andres ; Yoshihara, Toru ; Hagiwara, Masatoshi
Subjects: Alzheimer Disease - metabolism ; Alzheimer's disease ; Animals ; Antigens ; Astrocytes ; Astrocytes - metabolism ; Biological Sciences ; Cognitive ability ; Cognitive Dysfunction - metabolism ; Gene expression ; Glial cells ; Inflammation ; Inflammation - metabolism ; Mice ; Microglia ; Microglia - metabolism ; Neurodegeneration ; Neurodegenerative diseases ; Neuroinflammatory Diseases ; Neuronal-glial interactions ; Neurotoxicity ; NF-E2-Related Factor 2 - genetics ; NF-E2-Related Factor 2 - metabolism ; NF-kappa B - metabolism ; NF-κB protein ; Therapeutic targets
Is Part Of: Proceedings of the National Academy of Sciences - PNAS, 2023-08, Vol.120 (33), p.e2303809120-e2303809120
Description: Neuroinflammation is a common feature of neurodegenerative disorders such as Alzheimer's disease (AD). Neuroinflammation is induced by dysregulated glial activation, and astrocytes, the most abundant glial cells, become reactive upon neuroinflammatory cytokines released from microglia and actively contribute to neuronal loss. Therefore, blocking reactive astrocyte functions is a viable strategy to manage neurodegenerative disorders. However, factors or therapeutics directly regulating astrocyte subtypes remain unexplored. Here, we identified transcription factor NF-E2-related factor 2 (Nrf2) as a therapeutic target in neurotoxic reactive astrocytes upon neuroinflammation. We found that the absence of Nrf2 promoted the activation of reactive astrocytes in the brain tissue samples obtained from AD model 5xFAD mice, whereas enhanced Nrf2 expression blocked the induction of reactive astrocyte gene expression by counteracting NF-κB subunit p65 recruitment. Neuroinflammatory astrocytes robustly up-regulated genes associated with type I interferon and the antigen-presenting pathway, which were suppressed by Nrf2 pathway activation. Moreover, impaired cognitive behaviors observed in AD mice were rescued upon ALGERNON2 treatment, which potentiated the Nrf2 pathway and reduced the induction of neurotoxic reactive astrocytes. Thus, we highlight the potential of astrocyte-targeting therapy by promoting the Nrf2 pathway signaling for neuroinflammation-triggered neurodegeneration.
Publisher: United States: National Academy of Sciences
Language: English
Identifier: ISSN: 0027-8424
EISSN: 1091-6490
DOI: 10.1073/pnas.2303809120
PMID: 37549281
Source: Geneva Foundation Free Medical Journals at publisher websites
MEDLINE
PubMed Central

Back to results list


INSPIRE LIBRARY - TON DUC THANG UNIVERSITY	(84-028) 37 755 057	Feedback
19 Nguyen Huu Tho St. Dist.7, HCM	thuvien@tdtu.edu.vn	Feedback

Astrocyte-targeting therapy rescues cognitive impairment caused by neuroinflammation via the Nrf2 pathway

Copyright National Academy of Sciences Aug 15, 2023 ;Copyright © 2023 the Author(s). Published by PNAS. 2023 ;ISSN: 0027-8424 ;EISSN: 1091-6490 ;DOI: 10.1073/pnas.2303809120 ;PMID: 37549281

Searching Remote Databases, Please Wait