Soluble epoxide hydrolase as a therapeutic target for pain, inflammatory and neurodegenerative diseases
| Autor: | Bruce D. Hammock, William K. Schmidt, Karen Wagner, Cindy B. McReynolds |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Epoxide hydrolase 2 Inflammatory pain Pain Inflammation Neurodegenerative Pharmacology Neuropathic pain Article 03 medical and health sciences Lipoxygenase medicine Epoxy-fatty acids 2.1 Biological and endogenous factors Animals Humans Pharmacology (medical) Pharmacology & Pharmacy Aetiology Peripheral Neuropathy Neuroinflammation Epoxide Hydrolases biology Depression Chemistry Inflammatory and immune system Pain Research Fatty Acids Neurosciences Cytochrome P450 Neurodegenerative Diseases Pharmacology and Pharmaceutical Sciences Lipid signaling Alzheimer's disease Soluble epoxide hydrolase 030104 developmental biology Eicosanoid 5.1 Pharmaceuticals biology.protein Cyclooxygenase Chronic Pain Development of treatments and therapeutic interventions medicine.symptom |
| Zdroj: | Pharmacology & Therapeutics. 180:62-76 |
| ISSN: | 0163-7258 |
| Popis: | Eicosanoids are biologically active lipid signaling molecules derived from polyunsaturated fatty acids. Many of the actions of eicosanoid metabolites formed by cyclooxygenase and lipoxygenase enzymes have been characterized, however, the epoxy-fatty acids (EpFAs) formed by cytochrome P450 enzymes are newly described by comparison. The EpFA metabolites modulate a diverse set of physiologic functions that include inflammation and nociception among others. Regulation of EpFAs occurs primarily via release, biosynthesis and enzymatic transformation by the soluble epoxide hydrolase (sEH). Targeting sEH with small molecule inhibitors has enabled observation of the biological activity of the EpFAs in vivo in animal models, greatly contributing to the overall understanding of their role in the inflammatory response. Their role in modulating inflammation has been demonstrated in disease models including cardiovascular pathology and inflammatory pain, but extends to neuroinflammation and neuroinflammatory disease. Moreover, while the EpFA demonstrate activity against inflammatory pain, interestingly, this action extends to blocking chronic neuropathic pain as well. This review outlines the role of modulating sEH and the biological action of EpFA in models of pain and inflammatory diseases. |
| Databáze: | OpenAIRE |
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