Humble beginnings with big goals: Small molecule soluble epoxide hydrolase inhibitors for treating CNS disorders

Autor: Bruce D. Hammock, Diego Incontri, Sydney Zarriello, Samantha Schimmel, Cesar V. Borlongan, Sydney Corey, Mira Rajani, Anna Gorsky, Julian P. Tuazon
Rok vydání: 2019
Předmět:
0301 basic medicine
Epoxide hydrolase 2
Basic science
Central nervous system
Preclinical studies
Inflammation
Context (language use)
Neurodegenerative
Pharmacology
Epoxyeicosatrienoic acid
Article
03 medical and health sciences
chemistry.chemical_compound
Clinical trials
Druggability
0302 clinical medicine
Central Nervous System Diseases
TBI
Psychology
Animals
Humans
Medicine
Dementia
Enzyme Inhibitors
Epoxide Hydrolases
Neurology & Neurosurgery
business.industry
General Neuroscience
Neurosciences
medicine.disease
Brain Disorders
Stroke
030104 developmental biology
medicine.anatomical_structure
chemistry
5.1 Pharmaceuticals
Neurological
cardiovascular system
Cognitive Sciences
Development of treatments and therapeutic interventions
medicine.symptom
Stem cell
business
Neuroscience
030217 neurology & neurosurgery
Central Nervous System Agents
Zdroj: Progress in Neurobiology. 172:23-39
ISSN: 0301-0082
DOI: 10.1016/j.pneurobio.2018.11.001
Popis: Soluble epoxide hydrolase (sEH) degrades epoxides of fatty acids including epoxyeicosatrienoic acid isomers (EETs), which are produced as metabolites of the cytochrome P450 branch of the arachidonic acid pathway. EETs exert a variety of largely beneficial effects in the context of inflammation and vascular regulation. sEH inhibition is shown to be therapeutic in several cardiovascular and renal disorders, as well as in peripheral analgesia, via the increased availability of anti-inflammatory EETs. The success of sEH inhibitors in peripheral systems suggests their potential in targeting inflammation in the central nervous system (CNS) disorders. Here, we describe the current roles of sEH in the pathology and treatment of CNS disorders such as stroke, traumatic brain injury, Parkinson's disease, epilepsy, cognitive impairment, dementia and depression. In view of the robust anti-inflammatory effects of stem cells, we also outlined the potency of stem cell treatment and sEH inhibitors as a combination therapy for these CNS disorders. This review highlights the gaps in current knowledge about the pathologic and therapeutic roles of sEH in CNS disorders, which should guide future basic science research towards translational and clinical applications of sEH inhibitors for treatment of neurological diseases.
Databáze: OpenAIRE
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