Hydroxytyrosol Decreases LPS- and α-Synuclein-Induced Microglial Activation In Vitro.

Marta Gallardo-Fernández,José A. Rodríguez-Gómez,Rocío M. de Pablos,M. Carmen García-Parrilla,Ana M. Espinosa-Oliva,Ana M. Troncoso,José L. Venero,Ruth Hornedo-Ortega,Isabel M. Alonso-Bellido

doi:10.3390/antiox9010036

Abstract

Neuroinflammation is a common feature shared by neurodegenerative disorders, such as Parkinson’s disease (PD), and seems to play a key role in their development and progression. Microglia cells, the principal orchestrators of neuroinflammation, can be polarized in different phenotypes, which means they are able to have anti-inflammatory, pro-inflammatory, or neurodegenerative effects. Increasing evidence supports that the traditional Mediterranean dietary pattern is related to the reduction of cognitive decline in neurodegenerative diseases. A considerable intake of plant foods, fish, and extra virgin olive oil (EVOO), as well as a moderate consumption of red wine, all characteristic of the Mediterranean diet (MD), are behind these effects. These foods are especially rich in polyphenols, being the most relevant in the MD hydroxytyrosol (HT) and their derivatives present in EVOO, which have demonstrated a wide array of biological activities. Here, we demonstrate that HT is able to reduce the inflammation induced by two different stimuli: lipopolysaccharide and α-synuclein. We also study the possible molecular mechanisms involved in the anti-inflammatory effect of HT, including the study of nuclear factor kappa B (NF-κB), mitogen-activated protein kinases (MAPKs), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and inflammasome. Our data support the use of HT to prevent the inflammation associated with PD and shed light into the relationship between MD and this neurological disorder.

Highlights

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease, followingAlzheimer’s disease (AD)
There is strong evidence supporting that neuroinflammation is a pathological condition present in the central nervous system (CNS) leading to neuronal cell death of patients suffering from PD and AD [2]
The most compelling evidence supporting this view comes from multiple genome-wide association studies (GWAS), which have found a genetic association with PD risk including the human leukocyte antigen (HLA) region, tumor necrosis factor (TNF), TNFR1, and interleukin (IL)-1β, among others [3]

Summary

Introduction

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease, followingAlzheimer’s disease (AD). There is strong evidence supporting that neuroinflammation is a pathological condition present in the central nervous system (CNS) leading to neuronal cell death of patients suffering from PD and AD [2]. Microglial cell population plays a key role in brain immune response, defending, and maintaining homeostasis against diverse pathological situations. Brain neuroinflammation is orchestrated by microglial cells, the resident phagocytes that act as the initial responders to pathogens or tissue damage. LevelBethesda, of secondary antibody staining was previously subtracted to alllevel samples under and measured as the fold change of expression of NF-kB study. Background level of secondary antibody staining was previously subtracted to all samples under study. One-way analysis of variance (ANOVA) followed by. LSD± test forMeans post hoc multiple range. An alpha variance followed the LSD test for 3.0 post hoc multiple range comparisons

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