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

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Neurotherapeutics

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.

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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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Author notes

  1. Kang-Woo Lee

    Present address: Medical Research Division, Acupuncture, Moxibustion & Meridian Research Group, Korea Institute of Oriental Medicine, Daejeon, South Korea, 305-811

  2. Steven P. Braithwaite

    Present address: Circuit Therapeutics, Inc., Menlo Park, CA, 94025, USA

Authors and Affiliations

  1. Center for Neurodegenerative and Neuroimmunologic Diseases, Department of Neurology, UMDNJ-Robert Wood Johnson Medical School, 683 Hoes Lane West, Room 180, Piscataway, NJ, 08854, USA

    Kang-Woo Lee, Joo-Young Im, Jong-Min Woo, Hilary Grosso, Patricia K. Sonsalla, Eunsung Junn & M. Maral Mouradian

  2. Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, 32827, USA

    Yoon-Seong Kim & Ana Clara Cristovao

  3. Health Sciences Research Center, University of Beira Interior, Covilhã, Portugal

    Ana Clara Cristovao

  4. Department of Molecular Biology, Princeton University, Princeton, NJ, 08544, USA

    David S. Schuster, Marla M. Jalbut & Jeffry B. Stock

  5. Signum Biosciences, Inc., Monmouth Junction, NJ, 08852, USA

    Jose R. Fernandez, Michael Voronkov, Steven P. Braithwaite & Jeffry B. Stock

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  1. Kang-Woo Lee
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Correspondence to M. Maral Mouradian.

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Kang-Woo Lee and Joo-Young Im contributed equally to this work.

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Lee, KW., Im, JY., Woo, JM. et al. Neuroprotective and Anti-inflammatory Properties of a Coffee Component in the MPTP Model of Parkinson’s Disease. Neurotherapeutics 10, 143–153 (2013). https://doi.org/10.1007/s13311-012-0165-2

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