Soluble Epoxide Hydrolase and Brain Cholesterol Metabolism

Domingues, Michelle Flores; Callai-Silva, Natalia; Piovesan, Angela Regina; Carlini, Célia R.

doi:10.3389/fnmol.2019.00325

Cited by 16 publications

(18 citation statements)

References 83 publications

(106 reference statements)

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“…ACAT1 is an acetyl-coenzyme A acetyltransferase, which can catalyze the formation of cholesteryl esters from cholesterol and long-chain fatty acyl-CoAs [39]. EPHX2 is a member of the epoxide hydrolase family, and the N-terminal activity of EPHX2 can increase the cell's cholesterol level [40][41]. POR is a microsomal membrane-associated protein of two types: type I and type II, of which type II is responsible for cholesterol synthesis [42].…”

Section: Cholesterol Synthesismentioning

confidence: 99%

Integrated transcriptome and proteome analysis reveals potential mechanisms for differential abdominal fat deposition between divergently selected chicken lines

Wang

Leng

Ding

et al. 2021

Journal of Proteomics

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Background: Genetic selection for meat production performance of broilers concomitantly causes excessive abdominal fat deposition, accompanied by several adverse effects, such as the reduction of feed conversion e ciency and reproduction performance. Our previous studies have identi ed important genes regulating chicken fat deposition, using the Northeast Agricultural University broiler lines divergently selected for abdominal fat content (NEAUHLF) as an animal model. However, the molecular mechanism underlying fat deposition differences between fat and lean broilers remains largely unknown.Results: Here, we integrated the transcriptome (RNA-Seq) and quantitative proteome (isobaric tags for relative and absolute quantitation, iTRAQ) pro ling analyses on abdominal fat tissues from NEAUHLF chicken lines. Differentially expressed genes (466 DEGs) and proteins (231 DEPs) were identi ed, and enriched in pathways related to fatty acid metabolism, fatty acid biosynthesis, glycerophospholipid metabolism, and PPAR signaling, and in pathways mainly involved in protein processing, endocytosis and lipid metabolism, respectively. Moreover, several key DEGs and DEPs involved in long-chain fatty acid uptake, in situ lipogenesis (fatty acid and cholesterol synthesis), and lipid droplets accumulation were discovered, and most of them were up-regulated in the fat line, after integrated transcriptome and proteome analysis.Conclusions: Together, our ndings provided a novel insight into abdominal fat content discrepancy between the fat and lean chicken lines.

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Section: Cholesterol Synthesismentioning

confidence: 99%

Integrated transcriptome and proteome analysis reveals potential mechanisms for differential abdominal fat deposition between divergently selected chicken lines

Wang

Leng

Ding

et al. 2021

Journal of Proteomics

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“…The same is true for MDK, which binds directly to Aβ40 to inhibit its cytotoxicity in vitro [61] [64]. Ebselen, an irreversible inhibitor of EPHX2, has also been shown to decrease tau phosphorylation in a triple transgenic AD mouse model [63,65]. It has been suggested that oxidative stress can promote tau hyperphosphorylation and resultant aggregation and that inhibition of EPHX2 is anti-inflammatory [64].…”

Section: Log[m]mentioning

confidence: 96%

AD Informer Set: Chemical tools to facilitate Alzheimer’s disease drug discovery

Potjewyd

Annor-Gyamfi

Aubé³

et al. 2021

Preprint

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Introduction: The portfolio of novel targets to treat Alzheimer's disease (AD) has been enriched by the AMP-AD program. Methods: A cheminformatics-driven effort enabled identification of existing small molecule modulators for many protein targets nominated by AMP-AD and suitable positive control compounds to be included in the set. Results: We have built an annotated set of 171 small molecule modulators, including mostly inhibitors, targeting 98 unique proteins that have been nominated by AMP-AD consortium members as novel targets for AD treatment. These small molecules vary in their quality and should be considered chemical tools that can be used in efforts to validate therapeutic hypotheses, but which would require further optimization. A physical copy of the AD Informer Set can be ordered via the AD Knowledge Portal. Discussion: Small molecule tools that enable target validation are important tools for the translation of novel hypotheses into viable therapeutic strategies for AD.

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“…As mentioned, it is demonstrated that the sEH-phosphatase domain acts in cholesterol biosynthesis, reducing plasma cholesterol [118,122]. Several neurodegenerative hereditary diseases are associated with disturbances in cholesterol metabolism within the brain, such as Fabry disease, Niemann-Pick Type C disease, Gaucher disease, and GM1 and GM2 gangliosides [123][124][125].…”

Section: Seh-phosphatase Activity and Neurodegenerative Diseasesmentioning

confidence: 97%

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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Soluble Epoxide Hydrolase and Brain Cholesterol Metabolism

Cited by 16 publications

References 83 publications

Integrated transcriptome and proteome analysis reveals potential mechanisms for differential abdominal fat deposition between divergently selected chicken lines

Integrated transcriptome and proteome analysis reveals potential mechanisms for differential abdominal fat deposition between divergently selected chicken lines

AD Informer Set: Chemical tools to facilitate Alzheimer’s disease drug discovery

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

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