Evaluation of antiparkinson activity of PTUPB by measuring dopamine and its metabolites in Drosophila melanogaster: LC–MS/MS method development

Lakkappa, Navya; Krishnamurthy, Praveen Thaggikuppe; Yamjala, Karthik; Hwang, Sung Hee; Hammock, Bruce D.; Babu, B.

doi:10.1016/j.jpba.2017.11.043

Cited by 17 publications

(12 citation statements)

References 21 publications

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“…In PD models, 14,15-EET, which is released from astrocytes, enhances cell viability against oxidative stress [156] and protects DA neuronal loss in MPTP-treated mice [157]. Inhibition or KO of the soluble epoxide hydrolase (sEH, inhibition of which elevates endogenous EET) protects MPTP-treated mice [157,158], and a double sEH and COX-2 inhibitor has protective effects on a rotenone-induced Drosophila melanogaster PD model [159]. Combined, these findings suggest that EET has widespread neuroprotective effects, not necessarily relevant for PD only.…”

Section: Fatty Acylsmentioning

confidence: 99%

The Role of Lipids in Parkinson’s Disease

Xicoy

Wieringa

Martens

2019

Cells

179

161

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Parkinson’s disease (PD) is a neurodegenerative disease characterized by a progressive loss of dopaminergic neurons from the nigrostriatal pathway, formation of Lewy bodies, and microgliosis. During the past decades multiple cellular pathways have been associated with PD pathology (i.e., oxidative stress, endosomal-lysosomal dysfunction, endoplasmic reticulum stress, and immune response), yet disease-modifying treatments are not available. We have recently used genetic data from familial and sporadic cases in an unbiased approach to build a molecular landscape for PD, revealing lipids as central players in this disease. Here we extensively review the current knowledge concerning the involvement of various subclasses of fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterols, and lipoproteins in PD pathogenesis. Our review corroborates a central role for most lipid classes, but the available information is fragmented, not always reproducible, and sometimes differs by sex, age or PD etiology of the patients. This hinders drawing firm conclusions about causal or associative effects of dietary lipids or defects in specific steps of lipid metabolism in PD. Future technological advances in lipidomics and additional systematic studies on lipid species from PD patient material may improve this situation and lead to a better appreciation of the significance of lipids for this devastating disease.

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Section: Fatty Acylsmentioning

confidence: 99%

The Role of Lipids in Parkinson’s Disease

Xicoy

Wieringa

Martens

2019

Cells

179

161

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“…CYP epoxygenases may serve as the therapeutic targets of chronic cerebrovascular diseases and brain inflammatory disorders via blocking the vicious circle. EETs also inhibit oxidative stress and neuroinflammation to act its neuroprotective role, indicating that it has the potential to treat PD ( Lakkappa et al, 2016 ; Lakkappa et al, 2018 ; Huang et al, 2018 ). AA is also converted to anandamide, which can be further metabolized by brain CYP3A4, CYP4F2 and CYP2D6 ( Snider et al, 2010 ).…”

Section: The Roles Of Cytochrome P450s and Udp-glucuronosyltransferases In Endogenous Substancesmentioning

confidence: 99%

Alterations of Cytochrome P450s and UDP-Glucuronosyltransferases in Brain Under Diseases and Their Clinical Significances

Yun

Yang

et al. 2021

Front. Pharmacol.

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Cytochrome P450s (CYPs) and UDP-glucuronosyltransferases (UGTs) are both greatly important metabolic enzymes in various tissues, including brain. Although expressions of brain CYPs and UGTs and their contributions to drug disposition are much less than liver, both CYPs and UGTs also mediate metabolism of endogenous substances including dopamine and serotonin as well as some drugs such as morphine in brain, demonstrating their important roles in maintenance of brain homeostasis or pharmacological activity of drugs. Some diseases such as epilepsy, Parkinson’s disease and Alzheimer’s disease are often associated with the alterations of CYPs and UGTs in brain, which may be involved in processes of these diseases via disturbing metabolism of endogenous substances or resisting drugs. This article reviewed the alterations of CYPs and UGTs in brain, the effects on endogenous substances and drugs and their clinical significances. Understanding the roles of CYPs and UGTs in brain provides some new strategies for the treatment of central nervous system diseases.

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“…Therapeutic profile for sEHi in PD Drosophila melanogaster [168] Humble beginnings with big goals: Small molecule soluble epoxide hydrolase inhibitors for treating CNS disorders.…”

Section: Implication Of Seh In Pd Pathologymentioning

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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Evaluation of antiparkinson activity of PTUPB by measuring dopamine and its metabolites in Drosophila melanogaster: LC–MS/MS method development

Cited by 17 publications

References 21 publications

The Role of Lipids in Parkinson’s Disease

The Role of Lipids in Parkinson’s Disease

Alterations of Cytochrome P450s and UDP-Glucuronosyltransferases in Brain Under Diseases and Their Clinical Significances

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

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