Pesticide-Induced Gene Mutations and Parkinson Disease Risk: A Meta-Analysis

Liu, Xiaowei; Ma, Tao; Qu, Bo; Ji, Yan; Liu, Zhi

doi:10.1089/gtmb.2013.0313

Cited by 21 publications

(11 citation statements)

References 37 publications

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“…In patients with major depression, a significant association between a loss‐of‐function MDR1 (ABCB1) polymorphism and postural hypotension induced by nortriptyline, an MDR1 substrate, has been observed . In addition, MDR1 and BCRP also transport neurotoxic endogenous chemicals, including amyloid‐β as well as exogenous pesticides . Therefore, understanding the mechanisms by which BBB transporters are regulated is important for neuronal protection and drug efficacy in the brain.…”

Section: Introductionmentioning

confidence: 99%

Brain region‐specific regulation of histone acetylation and efflux transporters in mice

You

Shin

Mosaad

et al. 2019

J Biochem & Molecular Tox

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Multidrug resistance protein 1 (MDR1) and breast cancer resistance protein (BCRP) protect the brain by restricting the passage of chemicals across the blood-brain barrier. Prior studies have demonstrated the epigenetic regulation of MDR1 and BCRP in cancer cells treated with histone deacetylase (HDAC) inhibitors that enhance histone acetylation and gene transcription. In the present study, we tested the in vivo effects of two HDAC inhibitors, valproic acid (VPA; 400 mg/kg) and apicidin (5 mg/kg), on Mdr1 and Bcrp transporter expression in brain regions of adult male mice injected intraperitoneally daily for 7 days. VPA increased Mdr1 protein expression in the striatum (70%) and Bcrp protein in the midbrain (30%). Apicidin enhanced striatal Mdr1 protein (30%) and hippocampal Bcrp protein (20%).Transporter induction correlated with increased histone H3 acetylation in discrete brain regions. In conclusion, HDAC inhibitors upregulate transporter proteins in vivo, which may be important in regulating regional xenobiotic disposition within the brain.

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Section: Introductionmentioning

confidence: 99%

Brain region‐specific regulation of histone acetylation and efflux transporters in mice

You

Shin

Mosaad

et al. 2019

J Biochem & Molecular Tox

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“…Although, most cases of PD are idiopathic, many studies have implicated the accumulation of environmental neurotoxins and lack of efficient brain detoxification to the development of PD (Kalia and Lang, 2015). Because impaired function of drug transporters may be associated with brain accumulation of neurotoxins, genetic polymorphism in MDR1 gene has been suggested as a risk factor for PD (Liu et al, 2013; Zschiedrich et al, 2009). Moreover, reduction in the expression of P-gp has been reported in the endothelial cells of postmortem PD patients (Westerlund et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Regulation of ABC efflux transporters at blood-brain barrier in health and neurological disorders

et al. 2015

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The strength of the blood-brain barrier (BBB) in providing protection to the central nervous system from exposure to circulating chemicals is maintained by tight junctions between endothelial cells and by a broad range of transporter proteins that regulate exchange between CNS and blood. The most important transporters that restrict the permeability of large number of toxins as well as therapeutic agents are the ABC transporters. Among them, P-gp, BCRP, MRP1 and MRP2 are the utmost studied. These efflux transporters are neuroprotective, limiting the brain entry of neurotoxins; however, they could also restrict the entry of many therapeutics and contribute to CNS pharmacoresistance. Characterization of several regulatory pathways that govern expression and activity of ABC efflux transporters in the endothelium of brain capillaries have led to an emerging consensus that these processes are complex and contain several cellular and molecular elements. Alterations in ABC efflux transporters expression and/or activity occur in several neurological diseases. Here, we review the signaling pathways that regulate expression and transport activity of P-gp, BCRP, MRP1 and MRP2 as well as how their expression/activity changes in neurological diseases.

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“…A vér-agy gát detoxikáló hatásának csökkenésében az ott lokalizálódó pumpafehérjék csökkent expressziója, illetve aktivitása áll [62][63][64]. Az MDR1 gén genetikai polimorfizmusát is a Parkinson-kór rizikófaktorai közé sorolják [65,66].…”

Section: Parkinson-kórunclassified

Gyógyszertranszporterek szerepe a központi idegrendszerben

Temesszentandrási-Ambrus

Beéry

2016

Orvosi Hetilap

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Bár a vér-agy gát jelenlétét az emlősszervezetekben már a XX. század elején felismerték, pontos szerkezetét, illetve a benne található gyógyszertranszporter fehérjéket csak az utóbbi évtizedekben azonosították. A központi idegrendszer védelmét biztosító ATP-kötő kazettatranszporter pumpafehérjék mellett fontos szerepet játszanak az idegrendszer működésében a solute carrier transzporterek is, amelyek a táplálék-és energiaellátást biztosítják, illetve a metabolizmus során "eltakarító" funkciót is betöltenek. Az összefoglaló közlemény áttekintést ad az idegrendszerben előforduló főbb transzporter fehérjetípusokról, sejttípusonkénti lokalizációjukról, illetve a vizsgálatukra szolgáló főbb módszerekről. A közlemény második felében különböző neurodegeneratív betegségek és a patológiájukkal összefüg-gésbe hozható transzporter fehérjék kerülnek bemutatásra. Mindezek fényében olyan új terápiás stratégiák kerülhet-nek a figyelem középpontjába, amelyek a jelenleg gyógyíthatatlan betegségek esetében jelenthetnek majd megoldást. Orv. Hetil., 2016, 157(10), 370-378. Kulcsszavak: membrántranszporterek, vér-agy gát, neurodegeneratív betegségek, központi idegrendszer Role of drug transporters in the central nervous systemAlthough the presence of blood-brain barrier in the mammalian organisms was discovered in the early 1900s, its precise structure and the drug transporter proteins localized in the blood-brain barrier were identified only in the last decades. Beside the ATP-binding cassette transporter proteins responsible for the protection of the brain, the Solute Carrier transporters play also an important role in the function of the central nervous system by its feeding, energy supply and cleaning function during the metabolism. This review provides an overview on the main types of transporters located in the brain, on their localization in different cell types and the main techniques for their investigation. In the second part of this article various neurodegenerative disorders and the pathology-related transporter proteins are presented. In the light of recent experimental results new therapeutic strategies may come into the focus of research for the treatment of disorders currently without effective therapy. Rövidítések Aβ = béta-amiloid protein; ABC = ATP-binding cassette transporter; AIDS = acquired immunodeficiency syndrome; ALS = amyotrophiás lateralsclerosis; ANLSH = astrocyta-neuron laktát sönt hipotézis; ATP = adenozin-trifoszfát; BCRP = breast cancer resistance protein; Caco2 = caucasian colon adenocarcinoma cell line; CSF = cerebrospinal fluid; CTL = kolintranszporter; DAT = dopamintranszporter; EAAT = excitáns aminosav-transzporter; ECF = extracellular fluid; FDA = Food and Drug Administration; GABA = gamma-aminovajsav; GAT = GABA-transzporter; GLAST = glutamát-aszpartát transzporter; GLT = glutamáttranszporter; GLUT = glükóztranszpor-ter; GlyT = glicintranszporter; hCMEC/D3 = human cerebral microvascular endothelial cell line; HIV = human immunodeficiency virus; HMG-CoA = 3-hydroxy-3-methylglutaryl-coenzyme A; K...

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Pesticide-Induced Gene Mutations and Parkinson Disease Risk: A Meta-Analysis

Abstract: The current meta-analysis indicates that pesticide-induced gene mutations may contribute to increasing susceptibility to PD, especially in the GSTP1, SLC6A3, and MDR1 genes.

Cited by 21 publications

References 37 publications

Brain region‐specific regulation of histone acetylation and efflux transporters in mice

Brain region‐specific regulation of histone acetylation and efflux transporters in mice

Regulation of ABC efflux transporters at blood-brain barrier in health and neurological disorders

Gyógyszertranszporterek szerepe a központi idegrendszerben

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