title: Neuroprotective and anti-inflammatory properties of a coffee component in the MPTP model of Parkinson's disease.
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.
authors.affiliation: 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.
authors.forename: Kang-Woo
authors.initials: KW
authors.lastname: Lee
authors.forename: Joo-Young
authors.initials: JY
authors.lastname: Im
authors.forename: Jong-Min
authors.initials: JM
authors.lastname: Woo
authors.forename: Hilary
authors.initials: H
authors.lastname: Grosso
authors.forename: Yoon-Seong
authors.initials: YS
authors.lastname: Kim
authors.forename: Ana Clara
authors.initials: AC
authors.lastname: Cristovao
authors.forename: Patricia K
authors.initials: PK
authors.lastname: Sonsalla
authors.forename: David S
authors.initials: DS
authors.lastname: Schuster
authors.forename: Marla M
authors.initials: MM
authors.lastname: Jalbut
authors.forename: Jose R
authors.initials: JR
authors.lastname: Fernandez
authors.forename: Michael
authors.initials: M
authors.lastname: Voronkov
authors.forename: Eunsung
authors.initials: E
authors.lastname: Junn
authors.forename: Steven P
authors.initials: SP
authors.lastname: Braithwaite
authors.forename: Jeffry B
authors.initials: JB
authors.lastname: Stock
authors.forename: M Maral
authors.initials: MM
authors.lastname: Mouradian
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D003069:Coffee / Q000737:chemistry*; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D020267:MPTP Poisoning / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D003069:Coffee; D018696:Neuroprotective Agents; D010936:Plant Extracts