Fitxers
Tipus de document
ArticleVersió
Versió publicadaData de publicació
Llicència de publicació
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/227071
Soluble epoxide hydrolase inhibition improves Alzheimer’s disease hallmarks: correlation with peripheral inflammation and gut microbiota modulation
Títol de la revista
Director/Tutor
ISSN de la revista
Títol del volum
Recurs relacionat
Resum
Targeting brain inflammation has been proposed as a promising therapeutic strategy to cope with neurodegenerative diseases. Interestingly, accumulating data suggest that the gut microbiota partially exerts its neurodegenerative effects by exacerbating neuroinflammation through increased pathogenic or unhealthy genera that releases different types of cytokines in the periphery. Recently, soluble epoxide hydrolase enzyme (sEH) emerged as a new pharmacological approach for treating Alzheimer’s Disease. Treatment with a sEH inhibitor (UB-BJ-02) modified the gut microbiota in the 5xFAD mouse model, increasing health-promoting genera such as Lactobacillus and Limosilactobacillus. By contrast, pro-inflammatory genera (e.g., Bacteroides) were decreased. UB-BJ-02 treatment enhanced the production of anti-inflammatory peripheral mediators in the colon and spleen, such as Il-10. 5xFAD mice treated with UB-BJ-02 showed improved short- and long-term memory and spatial memory compared to 5xFAD control. Furthermore, we found a reduction in neuroinflammatory markers evaluated by immunohistochemical assays, such as GFAP and IBA-1, and gene expression, such as Il-1β, Tnf-a, Il-6, and Trem2, in the brain of 5xFAD-treated mice and a significant decrease in the number of Aβ plaques. T Treatment decreased DRP1 protein levels while increasing OPA1 levels, resulting in improved mitochondrial function corroborated by the elevation of Pgc1-α. Interestingly, a correlation between UB-BJ-02 brain effects and microbiota changes were demonstrated. To validate this correlation, we fed CL4176 AD transgenic strain, with Limosilactobacillus reuteri and Bacteroides rodentium. Consequently, we observed that changes in feeding modified the number of Aβ plaques and neuroinflammatory markers in C. elegans. Therefore, the present study suggested that sEH inhibition with UB-BJ-02 promoted neuroprotective effects, modulating gut microbiota and modifying peripheral and brain pro-inflammatory markers.
Matèries
Matèries (anglès)
Citació
Citació
JARNE FERRER, Júlia, et al. Soluble epoxide hydrolase inhibition improves Alzheimer’s disease hallmarks: correlation with peripheral inflammation and gut microbiota modulation. Aging And Disease. 2026. Vol. 17, num. 2, pags. 1131-1154. ISSN 2152-5250. [consulted: 7 of June of 2026]. Available at: https://hdl.handle.net/2445/227071