Olive Oil Polyphenols Can Be Useful to Prevent Aging-Associated Neurodegeneration

Journal of Alzheimer’s Parkinsonism & Dementia Review Article Olive Oil polyphenols can be Useful to Prevent Aging-Associated Neurodegeneration This article was published in the following Scient Open Access Journal: Journal of Alzheimer’s Parkinsonism & Dementia Received June 19, 2017; Accepted July 13, 2017; Published July 28, 2017 Fiorella Casamenti1* and Massimo Stefani2 Introduction to Alzheimer’s Disease 1Department Neuroscience, Psychology, Drug Research and Child Health, Division of Alzheimer’s disease (AD), the most common form of dementia affecting a large Pharmacology and Toxicology, Italy proportion of aged people in the developed countries, is considered a protein misfolding 2Department Clinical and Experimental Biomedical disease, and, as it is the case of other pathologies belonging to this group, at the present Sciences, University of Florence, Florence, Italy lacks effective therapy. The key histopathological sign of AD is the presence, in several of extracellular amyloid deposits (Aß) found in diffuse and senile plaques and around brain areas, of intracellular neurofibrillary tangles (NFT) of hyper phosphorylated tau, cerebral vessels and of dystrophic and degenerating neuritis [1]. Aβ plaque formation characterizeis considered AD relatively are thought specific to resultto AD primarilypathology; from however, the presence NFTs are of found plaque associated deposits with other disorders as well [2]. Functional alterations and behavioral deficits that whose main component is a polymeric fibrillar form of the 42 amino acid peptide (Aβ42) generated by proteolysis of the membrane amyloid precursor protein (APP) [3]. Among the different targets explored to treat AD, anti-Aβ approaches directed toward Aβ clearance and/or decreasing its production have shown promising results in animal models of AD [4]. tissue functional impairment and neuronal death has focused the importance, as the More recently, the interest in deciphering the relation between plaque burden, occurrencemain toxic species and to relieveto neurons, its symptoms of the oligomeric has shifted pre-fibrillar from the development assemblies originating of molecules at the onset of fibril growth [5]. Accordingly, the research of treatments able to delay AD toxic oligomeric intermediates. interfering with fibril growth to that of molecules able to counteract the appearance of Focusing dietary regimens associated with a reduced risk of AD in the aged inpopulation preventing can age-relatedbe useful to dysfunctions,find molecules cancer, exploitable neurodegenerative for AD prevention diseases and therapy. and in attenuatingMounting evidence AD-like pathologysupports andthe cognitivebeneficial deterioration. effects of the In Mediterranean particular, MD appearsdiet (MD) to be effective against mild cognitive impairment and its conversion to AD [6]. Olive Polyphenols and the Mediterranean Diet: Valuable Tools against Neurodegeneration The mediterranean diet provides many health benefits Many available data and population studies suggest that greater adherence to MD is [7],of particularly it enhances remarkable cognitive functionfor its health and benefits;reduces thein particular, risk of developing in addition mild to displaying cognitive ant diabetic, anticancer, antimicrobial, anti-inflammatory and anti-dislipidemic effects to the presence, in the MD, of the extra virgin olive oil (EVOO) and its polyphenols, as impairment and of its conversion to AD [6,8]. These findings have been better related shown by several population studies such as the PREDIMED-NAVARRA study [9-11] and *Corresponding Author: Fiorella Casamenti, by a number of clinical trials. The latter include a study carried out in Australia and New Department Neuroscience, Psychology, Zealand (ACTRN12613000602729), showing that a cause-effect relationship does exist Drug Research and Child Health, Division between MD and aging-dependent impairment of cognition [12]; another study, the of Pharmacology and Toxicology, Italy, Tel: +39552758286, Email: [email protected] Prevention con Dieta Mediterranea Nutrition Intervention Trial (ISRCTN35739639), led to conclude that a MD supplemented with olive oil or nuts is associated with a significant improvement of cognitive behavior in a population of aged people [13]. Volume 2 • Issue 1 • 012 www.scientonline.org J Alzheimers Parkinsonism Dementia Citation: Fiorella Casamenti, Massimo Stefani (2017). Olive Oil polyphenols can be Useful to Prevent Aging-Associated Neurodegeneration Page 2 of 6 is responsible for the burning sensation occurring in the throat Finally, the PREDIMED-NAVARRA randomized trial indicated that elenolic acid dialdehyde, p-HPEA-EDA, oleocanthal). The latter supporta MD intervention the idea that modulates the MD, theparticularly way genetic the prolongedfactors influence intake verbascoside, the caffeoylrhamnosylglucoside of HT, the lignans ofcognition its polyphenols, [14]. Overall, provide these populationconsistent andstudies effective and clinical protection trials 1-acetoxypinoresinolfollowing EVOO ingestion and pinoresinol. [27]. Other Amongolive polyphenols these polyphenols, include the most represented in olive oil are oleuropein, both in the glycated and in the aglycone forms, its main metabolite, against the risk of aging-associated neurodegeneration [15,16]. hydroxytyrosol, and oleocanthal. symptoms can result, at least in part, from its remarkable content of polyphenolsThe beneficial (sometimes effects of alsothe MDreferred against to theas biophenols) development arising of AD The content of polyphenols in EVOO can vary largely and and extra virgin olive oil. The polyphenols found in these aliments, cultivar, the ripening stage of the fruit, environmental factors, from the daily consumption of two typical components, red wine thecan extractionreach levels conditions, exceeding the 60 systemsmg/100 tog; itseparate depends oil on from the olive pastes and the storage conditions and time. The latter affect besides their known anti-oxidant effect, show several other spontaneous oxidation and the deposition of suspended particles. beneficial properties (see later). These include the ability to interfere positively with protein aggregationp inhibiting self-assembly of Molecular Mechanisms Underlying Protection of misfolded proteins/peptides into toxic amyloid oligomers and Olive Polyphenols against Neurodegeneration fibrils [17-19] and to affect cell roteostasis in several ways, including the modulation of protein degradation by the ubiquitin/ Modulation of the mTOR/AMPK pathways proteasome and/or the autophagic pathways (see later). Actually, plant, notably olive oil, polyphenols have been shown to andpossess of intracellularbeneficial effects tangles against of AD, the whose tau histopathological protein and signaturethe ensuing is the Most beneficial properties of EVOO polyphenols, notably OLE, presence of extracellular amyloid aggregates of the Aβ peptide have been associated, in addition to their well-known antioxidant power, to the modulation of several types of signaling pathways pathologic symptoms [18,20-23]. A possible beneficial effect of olive involving AMP-activated protein kinase (AMPK) and mammalian polyphenols against Parkinson disease has also been proposed [24]. Olive target of rapamycin mTOR, whose inhibition favors longevity and oil polyphenols have also been shown to be effective against insulin reduces inflammatory states [7,28]. As far as AMPK is concerned, resistance and impaired glucose regulation, two main symptoms it is well known its key role in AD pathogenesis [29]. mTOR is a underlying type 2 diabetes. Considering that increasing evidence potentcentral upstreamregulator ofinhibitors cell metabolism of autophagy, that finely and tunesthis inhibition the balance is supports a strong link between the main symptomsboth pathologiesof diabetes between anabolism and catabolism; it is also one of the most (mainlyat similar type molecular 2) and levels. AD-associated neurodegeneration [25,26] it is conceivable that olive polyphenols can interfere with removed following phosphorylation by AMPK [30]. However, the Olive tree polyphenols modulation by OLE of other neuronal signaling pathways, as it is theModulation case of resveratrol of cell proteostasis [31-33], cannot be excluded. characterizedNatural phenolic by the substances presence areof one secondary or more plant aromatic metabolites, rings p a major group of over 8000 plant compounds chemically Polyphenols, including the olive ones, are involved in regulation of belong to the phyto alexins family, including molecules cell roteostasis, including the ubiquitin/proteasome pathwayis andthe synthesizedwith one or moreby plants, hydroxyl often Substituent’s in leaves, [15].to combat Plant polyphenols pathogens majorthe autophagic proteolytic flux, complex, the latter and under increasing the control, evidence among indicates others, of the (bacteria, fungi) or to discourage leaf-eating insects. In the mTOR/AMPK machinery (see above) [34]. The proteasome family of Oleaceae, some polyphenols are highly concentrated that also in fruits before ripening, discouraging animals to eat fruits proteasomal function declines significantly with aging and in before their maturation for seed dispersal. The olive tree (Olea aging-related pathologies [35]. Plant polyphenols, including europaea oleuropein, can increase proteasome activity, with increased life span [36], together with the expression of proteasomal subunits ) produces a specific battery

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