Hydroxytyrosol improves mitochondrial energetics of a cellular model of Alzheimer’s disease

Abstract

Mitochondrial energetic deficit is one of the hallmarks of neurodegenerative disorders, e.g. Alzheimer´s disease (AD). Adherence to a Mediterranean diet is associated with lower incidence of cognitive decline and AD and extra virgin olive oil's (poly)phenols such as oleuropein and hydroxytyrosol (HT) are being actively studied in this respect. In this study, we assessed the effects of HT on mitochondrial energetic dysfunction in the 7PA2 cells cellular model, i.e. one of the best cellular models of Aβ toxicity with a well-characterized mitochondrial dysfunction typically observed in AD. We report an increase of new mitochondria at 8 h post HT-treatment, which was followed by higher mitochondrial fusion. Further, ATP concentrations were significantly increased after 24 h of treatment with HT as compared with controls. Our data suggest that HT may revert the energetic deficit of a cellular model of AD by potentiating mitochondrial activity. Because HT is being proposed as dietary supplement or component of functional foods, future studies in appropriate animal models andeventuallyhumans are warranted to further investigate its potential neuroprotective actions in AD.

Role of Hydroxytyrosol and Oleuropein in the Prevention of Aging and Related Disorders: Focus on Neurodegeneration, Skeletal Muscle Dysfunction and Gut Microbiota

“…As mentioned in the Section 5 , mitochondrial energetic deficit and altered energy metabolism are features of AD, and it turns out that HTyr is able to acutely induce mitochondria generation and fusion, in a model of Aβ toxicity and mitochondrial dysfunction (cell line 7PA2) [ 139 ]. Moreover, it has been shown that OLE and HTyr activate autophagy in SH-SY5Y cells exposed to toxic Aβ1–42 oligomers, thus preventing the accumulation of ROS and the impairment of mitochondrial function [ 140 ].…”

Biochemistry of Antioxidants: Mechanisms and Pharmaceutical Applications

“…The dietary administration of hydroxytyrosol was shown to promote the activity of mitochondria and reestablish the deficit of energy in the 7PA2 cell model of Alzheimer’s disease [ 169 ]. Likewise, González-Correa et al [ 170 ] reported that the supplementation of hydroxytyrosol also reduces the number of retinal ganglion cells in streptozotocin-diabetic rats.…”

Dietary Plant Polyphenols as the Potential Drugs in Neurodegenerative Diseases: Current Evidence, Advances, and Opportunities

“…As far as we know, mitochondrial dysfunction is one of the key cellular hallmarks of neurodegenerative diseases [246]. In the 7PA2 cell cellular model simulating Aβ toxicity of AD, hydroxytyrosol can restore the energy deficiency to maintain mitochondrial function [247]. Meanwhile, hydroxytyrosol ameliorates the neuronal impairment in APP/PS1 mice via modulating mitochondrial oxidative stress, neuroinflammation, and apoptosis [248].…”