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Neurotherapeutics

, Volume 10, Issue 1, pp 143–153 | Cite as

Neuroprotective and Anti-inflammatory Properties of a Coffee Component in the MPTP Model of Parkinson’s Disease

  • Kang-Woo Lee
  • Joo-Young Im
  • Jong-Min Woo
  • Hilary Grosso
  • Yoon-Seong Kim
  • Ana Clara Cristovao
  • Patricia K. Sonsalla
  • David S. Schuster
  • Marla M. Jalbut
  • Jose R. Fernandez
  • Michael Voronkov
  • Eunsung Junn
  • Steven P. Braithwaite
  • Jeffry B. Stock
  • M. Maral MouradianEmail author
Original Article

Abstract

Consumption of coffee is associated with reduced risk of Parkinson’s disease (PD), an effect that has largely been attributed to caffeine. However, coffee contains numerous components that may also be neuroprotective. One of these compounds is eicosanoyl-5-hydroxytryptamide (EHT), which ameliorates the phenotype of α-synuclein transgenic mice associated with decreased protein aggregation and phosphorylation, improved neuronal integrity and reduced neuroinflammation. Here, we sought to investigate if EHT has an effect in the MPTP model of PD. Mice fed a diet containing EHT for four weeks exhibited dose-dependent preservation of nigral dopaminergic neurons following MPTP challenge compared to animals given control feed. Reductions in striatal dopamine and tyrosine hydroxylase content were also less pronounced with EHT treatment. The neuroinflammatory response to MPTP was markedly attenuated, and indices of oxidative stress and JNK activation were significantly prevented with EHT. In cultured primary microglia and astrocytes, EHT had a direct anti-inflammatory effect demonstrated by repression of lipopolysaccharide-induced NFκB activation, iNOS induction, and nitric oxide production. EHT also exhibited a robust anti-oxidant activity in vitro. Additionally, in SH-SY5Y cells, MPP+-induced demethylation of phosphoprotein phosphatase 2A (PP2A), the master regulator of the cellular phosphoregulatory network, and cytotoxicity were ameliorated by EHT. These findings indicate that the neuroprotective effect of EHT against MPTP is through several mechanisms including its anti-inflammatory and antioxidant activities as well as its ability to modulate the methylation and hence activity of PP2A. Our data, therefore, reveal a strong beneficial effect of a novel component of coffee in multiple endpoints relevant to PD.

Keywords

Eicosanoyl-5-hydroxytryptamide Neuroprotection Anti-inflammatory Antioxidant Microglia Astrocytes 

Notes

Acknowledgments

This work was supported by a grant from Signum Biosciences and NIH grant AT006868 to M.M.M., who is the William Dow Lovett Professor of Neurology and is also supported by NIH grants NS059869 and NS073994. E.J. is supported by NIH grant NS070898. J.B.S. is supported in part by a grant from the American Parkinson Disease Association and by NIH grant AT006868.

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Supplementary material

13311_2012_165_MOESM1_ESM.pdf (551 kb)
ESM 1 (PDF 550 kb)

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Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2013

Authors and Affiliations

  • Kang-Woo Lee
    • 1
    • 6
  • Joo-Young Im
    • 1
  • Jong-Min Woo
    • 1
  • Hilary Grosso
    • 1
  • Yoon-Seong Kim
    • 2
  • Ana Clara Cristovao
    • 2
    • 3
  • Patricia K. Sonsalla
    • 1
  • David S. Schuster
    • 4
  • Marla M. Jalbut
    • 4
  • Jose R. Fernandez
    • 5
  • Michael Voronkov
    • 5
  • Eunsung Junn
    • 1
  • Steven P. Braithwaite
    • 5
    • 7
  • Jeffry B. Stock
    • 4
    • 5
  • M. Maral Mouradian
    • 1
    Email author
  1. 1.Center for Neurodegenerative and Neuroimmunologic Diseases, Department of NeurologyUMDNJ-Robert Wood Johnson Medical SchoolPiscatawayUSA
  2. 2.Burnett School of Biomedical Sciences, College of MedicineUniversity of Central FloridaOrlandoUSA
  3. 3.Health Sciences Research CenterUniversity of Beira InteriorCovilhãPortugal
  4. 4.Department of Molecular BiologyPrinceton UniversityPrincetonUSA
  5. 5.Signum Biosciences, Inc.Monmouth JunctionUSA
  6. 6.Medical Research Division, Acupuncture, Moxibustion & Meridian Research GroupKorea Institute of Oriental MedicineDaejeonSouth Korea
  7. 7.Circuit Therapeutics, Inc.Menlo ParkUSA

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