Abstract

Neurodegenerative diseases are driven by several mechanisms such as inflammation, abnormal protein aggregation, excitotoxicity, mitochondrial dysfunction and oxidative stress. So far, no therapeutic strategies are available for neurodegenerative diseases and in recent years the research is focusing on bioactive molecules present in food. In particular, extra-virgin olive oil (EVOO) phenols have been associated to neuroprotection. In this study, we investigated the potential antioxidant and neuroprotective activity of two different EVOO extracts obtained from Quercetano cultivar trees grown in two different areas (plain and hill) of the Tuscany region (Italy). The different geographical origin of the orchards influenced phenol composition. Plain extract presented a higher content of phenyl ethyl alcohols, cinnammic acids, oleacein, oleocanthal and flavones; meanwhile, hill extract was richer in lignans. Hill extract was more effective in protecting differentiated SH-SY5Y cells from peroxide stress thanks to a marked upregulation of the antioxidant enzymes heme oxygenase 1, NADPH quinone oxidoreductase 1, thioredoxin Reductase 1 and glutathione reductase. Proteomic analysis revealed that hill extract plays a role in the regulation of proteins involved in neuronal plasticity and activation of neurotrophic factors such as BDNF. In conclusion, these data demonstrate that EVOOs can have important neuroprotective activities, but these effects are strictly related to their specific phenol composition.

Highlights

  • We investigated the potential antioxidant and neuroprotective effects of two different extra-virgin olive oil (EVOO) extracts obtained from Quercetano cultivar trees grown in two different areas of the Tuscany region (Italy)

  • To better characterize the antioxidant mechanism underpinned by this higher protective activity of the hill extract, we evaluated the expression of four fundamental antioxidant enzymes, namely HMOX1, NQO1, TXNRD1 and GR

  • In consideration of the major proteome changes induced by treating SH-SY5Y cells with the hill extract, we focused our attention on related findings

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Summary

Introduction

The complexity of these diseases makes it difficult to fight them with single-target molecules. Neurodegenerative diseases represent an increasingly public health problem, especially in the aging population. These pathologies are multifactorial non communicable diseases driven by several but linked mechanisms such as inflammation, abnormal protein aggregation, excitotoxicity, oxidative stress and mitochondrial dysfunction [6,7,8,9,10]. Oxidative stress consists in an imbalance condition where the production of reactive species (mainly ROS) exceeds their detoxification, leading to an abnormal accumulation of radical species and oxidative damages. Regardless of how oxidative stress is caused, when encountered, cells counteract the damaging effect of this condition by activating the endogenous antioxidant defense system, which is compromised in the context of neurodegeneration

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