Abstract
(1) Background: Autophagy, the major cytoplasmic process of substrate turnover, declines with age, contributing to proteostasis decline, accumulation of harmful protein aggregates, damaged mitochondria and to ROS production. Accordingly, abnormalities in the autophagic flux may contribute to many different pathophysiological conditions associated with ageing, including neurodegeneration. Recent data have shown that extra-virgin olive oil (EVOO) polyphenols stimulate cell defenses against plaque-induced neurodegeneration, mainly, through autophagy induction. (2) Methods: We carried out a set of in vitro experiments on SH-SY5Y human neuroblastoma cells exposed to toxic Aβ1–42 oligomers to investigate the molecular mechanisms involved in autophagy activation by two olive oil polyphenols, oleuropein aglycone (OleA), arising from the hydrolysis of oleuropein (Ole), the main polyphenol found in olive leaves and drupes and its main metabolite, hydroxytyrosol (HT). (3) Results: Our data show that the mixture of the two polyphenols activates synergistically the autophagic flux preventing cell damage by Aβ1–42 oligomers., in terms of ROS production, and impairment of mitochondria. (4) Conclusion: Our results support the idea that EVOO polyphenols act synergistically in autophagy modulation against neurodegeneration. These data confirm and provide the rationale to consider these molecules, alone or in combination, as promising candidates to contrast ageing-associated neurodegeneration.
Highlights
IntroductionAlzheimer’s disease (AD), characterized by the development of neuronal amyloid-β (Aβ1–42 ) plaques and tau neurofibrillary tangles [1], accounted for 60 to 80% of dementia cases in 2015, affecting 46.8 million people worldwide [2], a number expected to double every 20 years, reaching 74.7 million in 2030 and 131.5 million in 2050 [3]
To investigate the pro-autophagic protective effect of oleuropein aglycone (OleA) against aggregates insults, we exposed our cells for 4 h and 24 h to a 75 μM OleA or HT concentration, by comparison, before the addition of Aβ1–42 aggregates (Supplementary Figure S1)
Sci. 2021, 22, 7225 we assessed the impact of the two polyphenols on autophagic activity and, considering that, in the intestine, the microflora decomposes a large fraction of OleA to HT, we sought to assess, in parallel, whether OleA/HT mixtures displayed synergistic activity on the autophagic path respect to the same amounts of each single component
Summary
Alzheimer’s disease (AD), characterized by the development of neuronal amyloid-β (Aβ1–42 ) plaques and tau neurofibrillary tangles [1], accounted for 60 to 80% of dementia cases in 2015, affecting 46.8 million people worldwide [2], a number expected to double every 20 years, reaching 74.7 million in 2030 and 131.5 million in 2050 [3]. The great majority of potential disease-modifying therapies clinical trials for AD yielded substantially negative results over the past 20 years. These trials tested a variety of treatments, including antioxidants, statins, non-steroidal anti-inflammatory drugs, estrogens and nerve growth factor gene therapy. Numerous longitudinal studies using several AD biomarkers indicated that AD develops decades before symptoms appearance [6,7], recommending the usefulness of preventive multi-target treatments aiming at hindering or delaying disease onset
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