| Literature DB >> 32488482 |
Christian Griñán-Ferré1, Sandra Codony2, Eugènia Pujol2, Jun Yang3, Rosana Leiva2, Carmen Escolano2, Dolors Puigoriol-Illamola4, Júlia Companys-Alemany4, Rubén Corpas5,6, Coral Sanfeliu5,6, Belen Pérez7, M Isabel Loza8, José Brea8, Christophe Morisseau3, Bruce D Hammock3, Santiago Vázquez9, Mercè Pallàs10, Carles Galdeano11.
Abstract
The inhibition of the enzyme soluble epoxide hydrolase (sEH) has demonstrated clinical therapeutic effects in several peripheral inflammatory-related diseases, with 3 compounds in 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). Evaluation of cognitive impairment and pathological hallmarks were used in 2 models of age-related cognitive decline and AD using 3 structurally different and potent sEH inhibitors as chemical probes. sEH is upregulated in brains from AD patients. Our findings supported the beneficial effects of central sEH inhibition, regarding reducing cognitive impairment, neuroinflammation, tau hyperphosphorylation pathology, and the number of amyloid plaques. This study suggests that inhibition of inflammation in the brain by targeting sEH is a relevant therapeutic strategy for AD.Entities:
Keywords: Druggability; Inflammation; Soluble epoxide hydrolase; Target engagement; Tau; β-amyloid
Year: 2020 PMID： 32488482 PMCID： PMC7851240 DOI： 10.1007/s13311-020-00854-1
Source DB: PubMed Journal: Neurotherapeutics ISSN： 1878-7479 Impact factor: 7.620