Title

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

Authors

Authors

K. W. Lee; J. Y. Im; J. M. Woo; H. Grosso; Y. S. Kim; A. C. Cristovao; P. K. Sonsalla; D. S. Schuster; M. M. Jalbut; J. R. Fernandez; M. Voronkov; E. Junn; S. P. Braithwaite; J. B. Stock;M. M. Mouradian

Comments

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Abbreviated Journal Title

PLoS One

Keywords

Eicosanoyl-5-hydroxytryptamide; Neuroprotection; Anti-inflammatory; Antioxidant; Microglia; Astrocytes; PROTEIN PHOSPHATASE 2A; ALPHA-SYNUCLEIN; REACTIVE OXYGEN; TYROSINE-HYDROXYLASE; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; MOUSE MODEL; CAFFEINE; ACTIVATION; MICROGLIA; Clinical Neurology; Neurosciences; Pharmacology & Pharmacy

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 alpha-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 NF kappa B 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.

Journal Title

Neurotherapeutics

Volume

Neurotherapeutics

Issue/Number

1

Publication Date

1-1-2013

Document Type

Review

Language

English

First Page

143

Last Page

153

WOS Identifier

10

ISSN

1933-7213

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