Soluble epoxide hydrolase as a stroke target

Abstract

Soluble epoxide hydrolase (sEH) is a promising therapeutic target for stroke. Both pharmacological inhibition and genetic knockout of sEH have shown protection in experimental models of cerebral ischemia. Additionally, human singlenucleotide polymorphisms in the gene that encodes for sEH, designated ephx2, have been correlated with stroke incidence and outcome. This chapter starts out by introducing sEH in the context of the five other mammalian epoxide hydrolases before delving specifically into sEH biology. Up-to-date research into sEH's protein structure, role in metabolizing epoxyeicosatrienoic acids, regional localization in brain, as well as subcellular localization are discussed in relation to brain function and disease. The chapter concludes by evaluating the prospect of using sEH inhibitors in clinical trials for the treatment of stroke based on the Stroke Therapy Academic and Industry Roundtable criteria.