Possible role of Epoxyeicosatrienoic acid in prevention of oxidative stress mediated neuroinflammation in Parkinson disorders

Lakkappa, Navya; Krishnamurthy, Praveen Thaggikuppe; Hammock, Bruce D.; Velmurugan, D.; Bharath, M. M. Srinivas

doi:10.1016/j.mehy.2016.06.003

Cited by 20 publications

(17 citation statements)

References 69 publications

(69 reference statements)

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“…Furthermore 14,15 EET administration protected dopaminergic neurons in mice treated with MPTP. Thus, because of the role neuroinflammation and mitochondrial dysfunction play in PD and the efficacy in preclinical models, it is hypothesized that sEH inhibition may have potential benefit in this condition in humans (Lakkappa, et al, 2016). …”

Section: Seh As a Target For Neurodegenerative Diseasesmentioning

confidence: 99%

Soluble epoxide hydrolase as a therapeutic target for pain, inflammatory and neurodegenerative diseases

Wagner

McReynolds

Schmidt

et al. 2017

Pharmacology & Therapeutics

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217

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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.

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Section: Seh As a Target For Neurodegenerative Diseasesmentioning

confidence: 99%

Soluble epoxide hydrolase as a therapeutic target for pain, inflammatory and neurodegenerative diseases

Wagner

McReynolds

Schmidt

et al. 2017

Pharmacology & Therapeutics

Self Cite

217

204

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“…To sum up, the previously published results suggested that sEH inhibitors or deletion might be able to protect DA neurons from death. Thus, giving the role that neuroinflammation, OS, and mitochondrial dysfunction play in PD and the efficacy of inhibiting the activity of sEH in preclinical models, sEH is a putative new pharmacological target for the treatment of PD and other α-syn-related pathologies such as Lewis body disease (LBD) [142] (Figures 2 and 3).…”

Section: Soluble Epoxide Hydrolase In Parkinson's Diseasementioning

confidence: 99%

Soluble Epoxide Hydrolase Inhibition to Face Neuroinflammation in Parkinson’s Disease: A New Therapeutic Strategy

et al. 2020

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Neuroinflammation is a crucial process associated with the pathogenesis of neurodegenerative diseases, including Parkinson’s disease (PD). Several pieces of evidence suggest an active role of lipid mediators, especially epoxy-fatty acids (EpFAs), in the genesis and control of neuroinflammation; 14,15-epoxyeicosatrienoic acid (14,15-EET) is one of the most commonly studied EpFAs, with anti-inflammatory properties. Soluble epoxide hydrolase (sEH) is implicated in the hydrolysis of 14,15-EET to its corresponding diol, which lacks anti-inflammatory properties. Preventing EET degradation thus increases its concentration in the brain through sEH inhibition, which represents a novel pharmacological approach to foster the reduction of neuroinflammation and by end neurodegeneration. Recently, it has been shown that sEH levels increase in brains of PD patients. Moreover, the pharmacological inhibition of the hydrolase domain of the enzyme or the use of sEH knockout mice reduced the deleterious effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration. This paper overviews the knowledge of sEH and EETs in PD and the importance of blocking its hydrolytic activity, degrading EETs in PD physiopathology. We focus on imperative neuroinflammation participation in the neurodegenerative process in PD and the putative therapeutic role for sEH inhibitors. In this review, we also describe highlights in the general knowledge of the role of sEH in the central nervous system (CNS) and its participation in neurodegeneration. We conclude that sEH is one of the most promising therapeutic strategies for PD and other neurodegenerative diseases with chronic inflammation process, providing new insights into the crucial role of sEH in PD pathophysiology as well as a singular opportunity for drug development.

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“…Cytochrome P450 3A4 (CYP3A4) expression promotes STAT3-mediated breast cancer cell growth via 14,15-EET [259]. EET analogs and sEH inhibitors are thought to have application in multiple diseases [260], such as Parkinson's [261], renal interstitial fibrosis in obstructive nephropathy [258], marrow or cord blood transplantation [262], inflammatory bowel disease-associated cancer [263], and other cancers [264,265].…”

Section: Epoxyeicosatrienoic Acids (Eets)mentioning

confidence: 99%

Eicosanoids in carcinogenesis

Brücher

Jamall

2019

4open

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Inflammation is the body's reaction to pathogenic (biological or chemical) stimuli and covers a burgeoning list of compounds and pathways that act in concert to maintain the health of the organism. Eicosanoids and related fatty acid derivatives can be formed from arachidonic acid and other polyenoic fatty acids via the cyclooxygenase and lipoxygenase pathways generating a variety of pro- and anti-inflammatory mediators, such as prostaglandins, leukotrienes, lipoxins, resolvins and others. The cytochrome P450 pathway leads to the formation of hydroxy fatty acids, such as 20-hydroxyeicosatetraenoic acid, and epoxy eicosanoids. Free radical reactions induced by reactive oxygen and/or nitrogen free radical species lead to oxygenated lipids such as isoprostanes or isolevuglandins which also exhibit pro-inflammatory activities. Eicosanoids and their metabolites play fundamental endocrine, autocrine and paracrine roles in both physiological and pathological signaling in various diseases. These molecules induce various unsaturated fatty acid dependent signaling pathways that influence crosstalk, alter cell–cell interactions, and result in a wide spectrum of cellular dysfunctions including those of the tissue microenvironment. Although the complete role of eicosanoids, including that of the recently elucidated anti-inflammatory specialized pro-resolving lipid mediators (SPMs), e.g. lipoxins, resolvins, protectins and maresins, is not completely understood, the result of unremitting chronic inflammation is fostering early stages of carcinogenesis. Chronic inflammation facilitates the transition from a normal cell to a cancerous one. The disruption of homeostasis across a wide, but identifiable, swath of diverse molecular pathways creates a micromilieu which constitutes an early and necessary step in the 6-step sequence of carcinogenesis for the vast majority of cancers, termed “sporadic cancers”.

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Possible role of Epoxyeicosatrienoic acid in prevention of oxidative stress mediated neuroinflammation in Parkinson disorders

Cited by 20 publications

References 69 publications

Soluble epoxide hydrolase as a therapeutic target for pain, inflammatory and neurodegenerative diseases

Soluble epoxide hydrolase as a therapeutic target for pain, inflammatory and neurodegenerative diseases

Soluble Epoxide Hydrolase Inhibition to Face Neuroinflammation in Parkinson’s Disease: A New Therapeutic Strategy

Eicosanoids in carcinogenesis

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