A Proteomic Approach to Uncover Neuroprotective Mechanisms of Oleocanthal against Oxidative Stress

Abstract

Neurodegenerative diseases represent a heterogeneous group of disorders that share common features like abnormal protein aggregation, perturbed Ca2+ homeostasis, excitotoxicity, impairment of mitochondrial functions, apoptosis, inflammation, and oxidative stress. Despite recent advances in the research of biomarkers, early diagnosis, and pharmacotherapy, there are no treatments that can halt the progression of these age-associated neurodegenerative diseases. Numerous epidemiological studies indicate that long-term intake of a Mediterranean diet, characterized by a high consumption of extra virgin olive oil, correlates with better cognition in aged populations. Olive oil phenolic compounds have been demonstrated to have different biological activities like antioxidant, antithrombotic, and anti-inflammatory activities. Oleocanthal, a phenolic component of extra virgin olive oil, is getting more and more scientific attention due to its interesting biological activities. The aim of this research was to characterize the neuroprotective effects of oleocanthal against H2O2-induced oxidative stress in neuron-like SH-SY5Y cells. Moreover, protein expression profiling, combined with pathways analyses, was used to investigate the molecular events related to the protective effects. Oleocanthal was demonstrated to counteract oxidative stress, increasing cell viability, reducing reactive oxygen species (ROS) production, and increasing reduced glutathione (GSH) intracellular level. Proteomic analysis revealed that oleocanthal significantly modulates 19 proteins in the presence of H2O2. In particular, oleocanthal up-regulated proteins related to the proteasome, the chaperone heat shock protein 90, the glycolytic enzyme pyruvate kinase, and the antioxidant enzyme peroxiredoxin 1. Moreover, oleocanthal protection seems to be mediated by Akt activation. These data offer new insights into the molecular mechanisms behind oleocanthal protection against oxidative stress.

Anticancer molecular mechanisms of oleocanthal

“…Finally, concerning the cooking procedures, Gomez-Alonso and associates (Gomez-Alonso, Fregapane, Salvador, & Gordon, 2003) observed a 20% degradation of OLC after 2 hr of frying at 180 C. Furthermore, OLC appears to be relatively stable upon heating at 240 C during 90 min (Cicerale, Conlan, Barnett, Sinclair, & Keast, 2009).…”

Health-promoting properties of oleocanthal and oleacein: Two secoiridoids from extra-virgin olive oil

“…OLC induces P-glycoprotein expression and functionality, which is responsible for β-amyloid clearance (Shinde et al 2015;Abuznait et al 2011;Qosa et al 2015). OLC also protects neurological cells from apoptosis, reducing ROS levels and upregulating Hsp90 and AKT, two proteins in charge of cell viability (Giusti et al 2018). OLC could be used as a complement in AD care, enhancing the effect of donepezil, a drug for AD treatment that helps to eliminate β-amyloid through the blood brain (Batarseh and Kaddoumi 2018).…”

Common Protective Strategies in Neurodegenerative Disease: Focusing on Risk Factors to Target the Cellular Redox System

“…Moreover, sulforaphane was able to counteract oxidative stress and to increase intracellular GSH levels and the expression, and activity, of glyoxalase 1 [ 236 , 237 ]. Bioactive substances from Olea europaea, such as oleocanthal and hydroxytyrosol, are able to counteract the glycation processes [ 238 , 239 ]; moreover, oleocanthal treatment improves GSH intracellular content and counteracts oxidative stress in neuron-like cell culture [ 240 ]. Recently, Angeloni et al analysed the relationship between oleocanthal and AD suggesting that, besides its effects to interfere with tau protein hyperphosphorylation and aggregation and its ability to induce A β efflux and clearance, it might counteract AD's progression by reducing glycation in the brain, thanks to its positive effect on the GSH level, and to its ability to decrease oxidative stress [ 241 ].…”