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Updated: Jul 29, 2025
09:58
Lipidomics and Transcriptomics in Neurological Diseases
Published on: March 18, 2022
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Cytochrome P450-derived eicosanoids in brain: From basic discovery to clinical translation
Catherine M Davis1, Aseel H Ibrahim2, Nabil J Alkayed3
1Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR, United States.
Advances in Pharmacology (San Diego, Calif.)
|May 26, 2023
Summary
Soluble epoxide hydrolase (sEH) enzyme activity increases in brain disorders, reducing protective epoxyeicosatrienoates (EETs). Inhibiting sEH offers a promising therapeutic strategy for neurological conditions like stroke and dementia.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Cytochrome P450 metabolism generates epoxyeicosatrienoates (EETs) and hydroxyeicosatetraenoates (HETEs) from arachidonic acid.
- Eicosanoids, including EETs and HETEs, have critical and contrasting roles in brain function and pathology.
- Soluble epoxide hydrolase (sEH) metabolizes EETs into less active diols, diminishing their beneficial effects.
Purpose of the Study:
- To review the role of P450 eicosanoids and their enzymes in brain health and disease.
- To summarize experimental and clinical studies targeting these pathways for neurological disorders.
- To discuss the potential of P450 eicosanoids and their enzymes as diagnostic biomarkers.
Main Methods:
- Review of existing literature on P450 eicosanoids in brain disorders.
- Analysis of studies investigating sEH inhibition as a therapeutic strategy.
- Evaluation of diagnostic utility of eicosanoids and related enzymes.
Main Results:
- Dysregulated EET levels, often due to increased sEH activity, are implicated in various brain diseases.
- sEH inhibition shows therapeutic promise for conditions such as stroke, dementia, subarachnoid hemorrhage, and epilepsy.
- Quantification of P450 eicosanoids and their enzymes may serve as valuable disease biomarkers.
Conclusions:
- Targeting the P450 eicosanoid pathway, particularly sEH inhibition, represents a significant therapeutic avenue for brain disorders.
- Translational research has made substantial progress in bringing these discoveries to clinical application.
- Further investigation into eicosanoid metabolism and enzyme activity can enhance diagnostic and therapeutic strategies for neurological diseases.
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