Epoxy hydrolyzedase inhibitors can reduce nerve inflammation and are expected to treat Alzheimer's disease

December 14, 2020 /--- neuroinvestitis is closely related to Alzheimer's disease (AD).
more and more people have come to realize that neuro-inflammation plays a key role in AD.
epoxy fatty acid (epFA) is a derivative of the peanut tyrene acid metabolic pathway and has anti-inflammatory activity.
, however, their efficacy is limited by the rapid hydrolyzing of EpFA by soluble epoxide hydrolyzase (sEH).
in a new study, researchers from Baylor College of Medicine in the United States reported that sEH is expressed primarily in astrogenic glial cells and elevates in posthumous brain tissue and 5xFAD β amyloid AD mouse models in AD patients.
the amount of sEH expressed in the brain in this AD mouse model was associated with a decrease in epiFA concentrations in the brain.
study was published in the September 2020 issue of the Journal of Science Translational Medicine under the title "An epoxide hydrolase resectionor reduces neuroinflammation in a mouse model of Alzheimer's disease".
synthesis of TPPU and its standard metabolites, pictured is Frontiers in Pharmacology, 2019, doi:10.3389/fphar.2019.00464.
by using a specific small molecule sEH inhibitor, i.e. 1-trifluoroxybenzene-3-(1-acrylamide-4-base) urea (1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea, TPPU), the authors report that in vivo, TPPU therapy protects wild mice from liposaccharin (LPS)-induced inflammation.
this result suggests that blocking sEH may supplement EpFA to combat nerve inflammation.
the long-term application of TPPU to this AD mouse model through drinking water can restore EpFA, reversing the resonant and immune pathogenic disorders of small glial and astrocyte cells.
this was β reduction in amyloid pathology and improvements in synact integrity and cognitive function in both behavioral tests.
TPPU therapy was associated with an increase in EpFA concentrations in the brains of this AD mouse model, confirming the brain penetration and target binding ability of this small molecule sEH inhibitor.
these findings support further research into TPPU as a potential therapeutic agent for AD.
, the study identified a lipid metabolism pathway that regulates neuroinflamm, supporting the further development of sEH inhibitors as a potential treatment for AD.
(Bioon.com) Reference: Anamitra Ghosh et al. An epoxide hydrolase inhibitor reduces neuroinflammation in a mouse model of Alzheimer's disease. Science Translational Medicine, 2020, doi:10.1126/scitranslmed.abb1206.