PT  - JOURNAL ARTICLE
AU  - Christian Griñán-Ferré
AU  - Sandra Codony
AU  - Eugènia Pujol
AU  - Jun Yang
AU  - Rosana Leiva
AU  - Carmen Escolano
AU  - Dolors Puigoriol-Illamola
AU  - Júlia Companys-Alemany
AU  - Rubén Corpas
AU  - Coral Sanfeliu
AU  - M. Isabel Loza
AU  - José Brea
AU  - Christophe Morisseau
AU  - Bruce D. Hammock
AU  - Santiago Vázquez
AU  - Mercè Pallàs
AU  - Carles Galdeano
TI  - Pharmacological inhibition of soluble epoxide hydrolase as a new therapy for Alzheimer’s Disease
AID  - 10.1101/605055
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 605055
4099  - http://biorxiv.org/content/early/2019/04/10/605055.short
4100  - http://biorxiv.org/content/early/2019/04/10/605055.full
AB  - The inhibition of the enzyme soluble epoxide hydrolase (sEH) has demonstrated clinical therapeutic effects in several peripheral inflammatory-related diseases, with two compounds that have entered clinical trials. However, the role of this enzyme in the neuroinflammation process has been largely neglected. Herein, we disclose the pharmacological validation of sEH as a novel target for the treatment of Alzheimer’s Disease (AD). Of interest, we have found that sEH is upregulated in brains from AD patients. We have evaluated the cognitive impairment and the pathological hallmarks in two models of age-related cognitive decline and AD using three structurally different and potent sEH inhibitors as chemical probes. Our findings supported our expectations on the beneficial effects of central sEH inhibition, regarding of reducing cognitive impairment, tau hyperphosphorylation pathology and the number of amyloid plaques. Interestingly, our results suggest that reduction of inflammation in the brain is a relevant therapeutic strategy for all stages of AD.