Serum metabolite signature of the modified Mediterranean-DASH intervention for neurodegenerative delay (MIND) diet.

INTRODUCTION: There is a lack of biomarkers of clinically important diets, such as the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet. OBJECTIVES: Our study explored serum metabolites associated with adherence to the MIND diet. METHODS: In 3,908 Atherosclerosis Risk in Communities (ARIC) study participants, we calculated a modified MIND diet score based on a 66-item self-reported food frequency questionnaire (FFQ). The modified score did not include berries and olive oil, as these items were not assessed in the FFQ. We used multivariable linear regression models in 2 subgroups of ARIC study participants and meta-analyzed results using fixed effects regression to identify significant metabolites after Bonferroni correction. We also examined associations between these metabolites and food components of the modified MIND diet. C-statistics evaluated the prediction of high modified MIND diet adherence using significant metabolites beyond participant characteristics. RESULTS: Of 360 metabolites analyzed, 27 metabolites (15 positive, 12 negative) were significantly associated with the modified MIND diet score (lipids, n = 13; amino acids, n = 5; xenobiotics, n = 3; cofactors and vitamins, n = 3; carbohydrates n = 2; nucleotide n = 1). The top 4 metabolites that improved the prediction of high dietary adherence to the modified MIND diet were 7-methylxanthine, theobromine, docosahexaenoate (DHA), and 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF). CONCLUSION: Twenty-seven metabolomic markers were correlated with the modified MIND diet. The biomarkers, if further validated, could be useful to objectively assess adherence to the MIND diet.

An Anti-Inflammatory Diet and Its Potential Benefit for Individuals with Mental Disorders and Neurodegenerative Diseases-A Narrative Review.

This narrative review synthesizes current evidence regarding anti-inflammatory dietary patterns and their potential benefits for individuals with mental disorders and neurodegenerative diseases. Chronic low-grade inflammation is increasingly recognized as a key factor in the etiology and progression of these conditions. The review examines the evidence for the anti-inflammatory and neuroprotective properties of dietary components and food groups, focusing on whole foods rather than specific nutrients or supplements. Key dietary components showing potential benefits include fruits and vegetables (especially berries and leafy greens), whole grains, legumes, fatty fish rich in omega-3, nuts (particularly walnuts), olive oil, and fermented foods. These foods are generally rich in antioxidants, dietary fiber, and bioactive compounds that may help modulate inflammation, support gut health, and promote neuroprotection. Conversely, ultra-processed foods, red meat, and sugary beverages may be harmful. Based on this evidence, we designed the Brain Anti-Inflammatory Nutrition (BrAIN) diet. The mechanisms of this diet include the modulation of the gut microbiota and the gut-brain axis, the regulation of inflammatory pathways, a reduction in oxidative stress, and the promotion of neuroplasticity. The BrAIN diet shows promise as an aid to manage mental and neurodegenerative disorders.

Exploration of dietary interventions to treat mitochondrial fatty acid disorders in a mouse model.

Mitochondrial fatty acids synthesis (mtFAS) is a conserved metabolic pathway essential for mitochondrial respiration. The best characterized mtFAS product is the medium-chain fatty acid octanoate (C8) used as a substrate in the synthesis of lipoic acid (LA), a cofactor required by several mitochondrial enzyme complexes. In humans, mutations in the mtFAS component enoyl reductase MECR cause childhood-onset neurodegenerative disorder MEPAN. A complete deletion of Mecr in mice is embryonically lethal, while selective deletion of Mecr in cerebellar Purkinje cells causes neurodegeneration in these cells. A fundamental question in the research of mtFAS deficiency is if the defect is amenable to treatment by supplementation with known mtFAS products. Here we used the Purkinje-cell specific mtFAS deficiency neurodegeneration model mice to study if feeding the mice with a medium-chain triacylglycerol-rich formula supplemented with LA could slow down or prevent the neurodegeneration in Purkinje cell-specific Mecr KO mice. Feeding started at the age of 4 weeks and continued until the age of 9 months. The neurological status on the mice was assessed at the age of 3, 6, and 9 months with behavioral tests and the state of the Purkinje cell deterioration in the cerebellum was studied histologically. We showed that feeding the mice with medium chain triacylglycerols and LA affected fatty acid profiles in the cerebellum and plasma but did not prevent the development of neurodegeneration in these mice. Our results indicate that dietary supplementation with medium chain fatty acids and LA alone is not an efficient way to treat mtFAS disorders.

The Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) Diet for the Aging Brain: A Systematic Review.

The Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet seems a promising approach to preserve brain function during aging. Previous systematic reviews have demonstrated benefits of the MIND diet for cognition and dementia, though an update is needed. Additionally, other outcomes relevant to brain aging have not been summarized. Therefore, this systematic review aims to give an up-to-date and complete overview on human studies that examined the MIND diet in relation to brain aging outcomes in adults aged ≥40 y. Ovid Medline, Web of Science core collection, and Scopus were searched up to July 25, 2023. Study quality was assessed using the Newcastle-Ottawa Scale and the Cochrane Risk-of-Bias tool. We included 40 articles, of which 32 were unique cohorts. Higher MIND diet adherence was protective of dementia in 7 of 10 cohorts. Additionally, positive associations were demonstrated in 3 of 4 cohorts for global cognition and 4 of 6 cohorts for episodic memory. The protective effects of the MIND diet on cognitive decline are less apparent, with only 2 of 7 longitudinal cohorts demonstrating positive associations for global decline and 1 of 6 for episodic memory decline. For other brain outcomes (domain-specific cognition, cognitive impairments, Parkinson's disease, brain volume, and pathology), results were mixed or only few studies had been performed. Many of the cohorts demonstrating protective associations were of North American origin, raising the question if the most favorable diet for healthy brain aging is population-dependent. In conclusion, this systematic review provides observational evidence for protective associations between the MIND diet and global cognition and dementia risk, but evidence for other brain outcomes remains mixed and/or limited. The MIND diet may be the preferred diet for healthy brain aging in North American populations, though evidence for other populations seems less conclusive. This review was registered at PROSPERO as CRD42022254625.

Impact of Pharmacological and Non-Pharmacological Modulators on Dendritic Spines Structure and Functions in Brain.

Dendritic spines are small, thin, hair-like protrusions found on the dendritic processes of neurons. They serve as independent compartments providing large amplitudes of Ca2+ signals to achieve synaptic plasticity, provide sites for newer synapses, facilitate learning and memory. One of the common and severe complication of neurodegenerative disease is cognitive impairment, which is said to be closely associated with spine pathologies viz., decreased in spine density, spine length, spine volume, spine size etc. Many treatments targeting neurological diseases have shown to improve the spine structure and distribution. However, concise data on the various modulators of dendritic spines are imperative and a need of the hour. Hence, in this review we made an attempt to consolidate the effects of various pharmacological (cholinergic, glutamatergic, GABAergic, serotonergic, adrenergic, and dopaminergic agents) and non-pharmacological modulators (dietary interventions, enriched environment, yoga and meditation) on dendritic spines structure and functions. These data suggest that both the pharmacological and non-pharmacological modulators produced significant improvement in dendritic spine structure and functions and in turn reversing the pathologies underlying neurodegeneration. Intriguingly, the non-pharmacological approaches have shown to improve intellectual performances both in preclinical and clinical platforms, but still more technology-based evidence needs to be studied. Thus, we conclude that a combination of pharmacological and non-pharmacological intervention may restore cognitive performance synergistically via improving dendritic spine number and functions in various neurological disorders.

Involvement of Microglia in Neurodegenerative Diseases: Beneficial Effects of Docosahexahenoic Acid (DHA) Supplied by Food or Combined with Nanoparticles.

Neurodegenerative diseases represent a major public health issue and require better therapeutic management. The treatments developed mainly target neuronal activity. However, an inflammatory component must be considered, and microglia may constitute an important therapeutic target. Given the difficulty in developing molecules that can cross the blood-brain barrier, the use of food-derived molecules may be an interesting therapeutic avenue. Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid (22:6 omega-3), has an inhibitory action on cell death and oxidative stress induced in the microglia. It also acts on the inflammatory activity of microglia. These data obtained in vitro or on animal models are corroborated by clinical trials showing a protective effect of DHA. Whereas DHA crosses the blood-brain barrier, nutritional intake lacks specificity at both the tissue and cellular level. Nanomedicine offers new tools which favor the delivery of DHA at the cerebral level, especially in microglial cells. Because of the biological activities of DHA and the associated nanotargeting techniques, DHA represents a therapeutic molecule of interest for the treatment of neurodegenerative diseases.

Effects of Nutrients on Platelet Function: A Modifiable Link between Metabolic Syndrome and Neurodegeneration?

Metabolic syndrome increases the risk of vascular dementia and other neurodegenerative disorders. Recent studies underline that platelets play an important role in linking peripheral with central metabolic and inflammatory mechanisms. In this narrative review, we address the activation of platelets in metabolic syndrome, their effects on neuronal processes and the role of the mediators (e.g., serotonin, platelet-derived growth factor). Emerging evidence shows that nutritional compounds and their metabolites modulate these interactions-specifically, long chain fatty acids, endocannabinoids and phenolic compounds. We reviewed the role of activated platelets in neurovascular processes and nutritional compounds in platelet activation.

Mediterranean Diet and Neurodegenerative Diseases: The Neglected Role of Nutrition in the Modulation of the Endocannabinoid System.

Neurodegenerative disorders are a widespread cause of morbidity and mortality worldwide, characterized by neuroinflammation, oxidative stress and neuronal depletion. The broad-spectrum neuroprotective activity of the Mediterranean diet is widely documented, but it is not yet known whether its nutritional and caloric balance can induce a modulation of the endocannabinoid system. In recent decades, many studies have shown how endocannabinoid tone enhancement may be a promising new therapeutic strategy to counteract the main hallmarks of neurodegeneration. From a phylogenetic point of view, the human co-evolution between the endocannabinoid system and dietary habits could play a key role in the pro-homeostatic activity of the Mediterranean lifestyle: this adaptive balance among our ancestors has been compromised by the modern Western diet, resulting in a "clinical endocannabinoid deficiency syndrome". This review aims to evaluate the evidence accumulated in the literature on the neuroprotective, immunomodulatory and antioxidant properties of the Mediterranean diet related to the modulation of the endocannabinoid system, suggesting new prospects for research and clinical interventions against neurodegenerative diseases in light of a nutraceutical paradigm.

Neuro-nutraceutical potential of Asparagus racemosus: A review.

Debilitating neuropsychiatric and neurodegenerative conditions are associated with complex multifactorial pathophysiology. Their treatment strategies often only provide symptomatic relief, delaying disease progression without giving a complete cure. Potent and safer treatment alternatives beyond symptomatic relief are sought. Herbal supplements have surely been explored due to their multiple component nature to enhance the effect of western medications. One such well-documented nutraceutical in the ancient Greek, Chinese, and Ayurvedic medicine system known for its various medicinal benefits is Asparagus racemosus. Widely used for its lactogenic properties, A. racemosus is also cited in Ayurveda as a nervine tonic. A. racemosus based nutraceuticals have shown to possess adaptogenic, neuroprotective, antioxidant, anti-inflammatory, and nootropic activity under preclinical and clinical settings without posing significant adverse effects. A. racemosus extracts restore the perturbed neurotransmitters and prevent oxidative neuronal damage. From the available neuropharmacological researches, the physiological actions of A. racemosus can ultimately be directed for either augmentation of cognitive ability or in the management of neurological conditions such as stress, anxiety, depression, epilepsy, Parkinson's, and Alzheimer's disease. The studies focus on the multi-component extract, and the lack of standardization has been a major hurdle in preventing the allotment of reported neuropharmacological activity to one of the phytoconstituent. Herbal standardization of the plant extract based on a specific biomarker can help elucidate the intricate biomolecular pathway and neurocircuitries being involved. This, followed by rigorous standardized clinical trials, fixing dosages, and determining contraindications would facilitate the translation of A. racemosus to a FDA-approved neuromedicine for neurological disorders.

Morin hydrate: A comprehensive review on novel natural dietary bioactive compound with versatile biological and pharmacological potential.

Flavonoids are natural plant-derived dietary bioactive compounds having a substantial impact on human health. Morin hydrate is a bioflavonoid mainly obtained from fruits, stem, and leaves of Moraceae family members' plants. Plenty of evidences supported that morin hydrate exerts its beneficial effects against various chronic and life-threatening degenerative diseases. Our current article discloses the recent advances that have been studied to explore the biological/pharmacological properties and molecular mechanisms to better understand the beneficial and multiple health benefits of morin hydrate. Indeed, Morin hydrate exerts free radical scavenging, antioxidant, anti-inflammatory, anti-cancerous, anti-microbial, antidiabetic, anti-arthritis, cardioprotective, neuroprotective, nephroprotective, and hepatoprotective effects. Moreover, morin hydrate exhibits its pharmacological activities by modulating various cellular signaling pathways such as Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-қB), Mitogen-activated protein kinase (MAPK), Janus kinases/ Signal transducer and activator of transcription proteins (JAKs/STATs), Kelch-like ECH-associated protein1/Nuclear erythroid-2-related factor (Keap1/Nrf2), Endoplasmic reticulum (ER), Mitochondrial-mediated apoptosis, Wnt/ß-catenin, and Mechanistic target of rapamycin (mTOR). Most importantly, morin hydrate has the potential to modulate a variety of biological networks. Therefore, it can be predicted that this therapeutically potent compound could serve as a dietary agent for the expansion of human health and might be helpful for the development of the novel drug in the future. However, due to the lack of clinical trials, special human clinical trials are needed to address the effects of morin hydrate on various life-threatening disparities to recommend morin and/or morin-rich foods with other foods or bioactive dietary components, as well as dose-response interaction and safety profile.

The Seaweed Diet in Prevention and Treatment of the Neurodegenerative Diseases.

Edible marine algae are rich in bioactive compounds and are, therefore, a source of bioavailable proteins, long chain polysaccharides that behave as low-calorie soluble fibers, metabolically necessary minerals, vitamins, polyunsaturated fatty acids, and antioxidants. Marine algae were used primarily as gelling agents and thickeners (phycocolloids) in food and pharmaceutical industries in the last century, but recent research has revealed their potential as a source of useful compounds for the pharmaceutical, medical, and cosmetic industries. The green, red, and brown algae have been shown to have useful therapeutic properties in the prevention and treatment of neurodegenerative diseases: Parkinson, Alzheimer's, and Multiple Sclerosis, and other chronic diseases. In this review are listed and described the main components of a suitable diet for patients with these diseases. In addition, compounds derived from macroalgae and their neurophysiological activities are described.

Thiamine Pyrophosphokinase Deficiency due to Mutations in the TPK1 Gene: A Rare, Treatable Neurodegenerative Disorder.

TPK deficiency due to TPK1 mutations is a rare neurodegenerative disorder, also known as thiamine metabolism dysfunction syndrome 5 (OMIM no.: 614458). Here, we report a new patient with compound heterozygous TPK1 mutations, of which one has not been described so far. The individual reported here suffered from acute onset encephalopathy, ataxia, muscle hypotonia, and regression of developmental milestones in early infancy, repeatedly triggered by febrile infections. Initiation of high-dose thiamine and magnesium supplementation led to a marked and sustained improvement of alertness, ataxia, and muscle tone within days. Contrary to the described natural history of patients with TPK deficiency, the disease course was favorable under thiamine treatment without deterioration or developmental regression during the follow-up period. TPK deficiency is a severe neurodegenerative disease. This case report demonstrates that this condition is potentially treatable. High-dose thiamine treatment should therefore be initiated immediately after diagnosis or even upon suspicion.

Serum Metabolomics Profiling of Commercially Mixed Functional Foods-Effects in Beta-Amyloid Induced Rats Measured Using 1H NMR Spectroscopy.

Functional foods such as pomegranate, dates and honey were shown by various previous studies to individually have a neuroprotective effect, especially in neurodegenerative disease such as Alzheimer's disease (AD). In this novel and original study, an 1H NMR spectroscopy tool was used to identify the metabolic neuroprotective mechanism of commercially mixed functional foods (MFF) consisting of pomegranate, dates and honey, in rats injected with amyloid-beta 1-42 (Aß-42). Forty-five male albino Wistar rats were randomly divided into five groups: NC (0.9% normal saline treatment + phosphate buffer solution (PBS) solution injection), Abeta (0.9% normal saline treatment + 0.2 µg/µL Aß-42 injection), MFF (4 mL/kg MFF treatment + PBS solution injection), Abeta-MFF (4 mL/kg MFF treatment + 0.2 µg/µL Aß-42 injection) and Abeta-NAC (150 mg/kg N-acetylcysteine + 0.2 µg/µL Aß-42 injection). Based on the results, the MFF and NAC treatment improved the spatial memory and learning using Y-maze. In the metabolic analysis, a total of 12 metabolites were identified, for which levels changed significantly among the treatment groups. Systematic metabolic pathway analysis found that the MFF and NAC treatments provided a neuroprotective effect in Aß-42 injected rats by improving the acid amino and energy metabolisms. Overall, this finding showed that MFF might serve as a potential neuroprotective functional food for the prevention of AD.

Palmitoylethanolamide: A Nutritional Approach to Keep Neuroinflammation within Physiological Boundaries-A Systematic Review.

Neuroinflammation is a physiological response aimed at maintaining the homodynamic balance and providing the body with the fundamental resource of adaptation to endogenous and exogenous stimuli. Although the response is initiated with protective purposes, the effect may be detrimental when not regulated. The physiological control of neuroinflammation is mainly achieved via regulatory mechanisms performed by particular cells of the immune system intimately associated with or within the nervous system and named "non-neuronal cells." In particular, mast cells (within the central nervous system and in the periphery) and microglia (at spinal and supraspinal level) are involved in this control, through a close functional relationship between them and neurons (either centrally, spinal, or peripherally located). Accordingly, neuroinflammation becomes a worsening factor in many disorders whenever the non-neuronal cell supervision is inadequate. It has been shown that the regulation of non-neuronal cells-and therefore the control of neuroinflammation-depends on the local "on demand" synthesis of the endogenous lipid amide Palmitoylethanolamide and related endocannabinoids. When the balance between synthesis and degradation of this bioactive lipid mediator is disrupted in favor of reduced synthesis and/or increased degradation, the behavior of non-neuronal cells may not be appropriately regulated and neuroinflammation exceeds the physiological boundaries. In these conditions, it has been demonstrated that the increase of endogenous Palmitoylethanolamide-either by decreasing its degradation or exogenous administration-is able to keep neuroinflammation within its physiological limits. In this review the large number of studies on the benefits derived from oral administration of micronized and highly bioavailable forms of Palmitoylethanolamide is discussed, with special reference to neuroinflammatory disorders.

Evaluating the Effects of Grain of Isogenic Wheat Lines Differing in the Content of Anthocyanins in Mouse Models of Neurodegenerative Disorders.

Functional foods enriched with plant polyphenols and anthocyanins in particular attract special attention due to multiple beneficial bioactive properties of the latter. We evaluated the effects of a grain diet rich in anthocyanins in a mouse model of Alzheimer's disease induced by amyloid-beta (Aß) and a transgenic mouse model of Parkinson's disease (PD) with overexpression of human alpha-synuclein. The mice were kept at a diet that consisted of the wheat grain of near isogenic lines differing in anthocyanin content for five-six months. The anthocyanin-rich diet was safe and possessed positive effects on cognitive function. Anthocyanins prevented deficits in working memory induced by Aß or a long-term grain mono-diet; they partially reversed episodic memory alterations. Both types of grain diets prolonged memory extinction and rescued its facilitation in the PD model. The dynamics of the extinction in the group fed with the anthocyanin-rich wheat was closer to that in a group of wild-type mice given standard chow. The anthocyanin-rich diet reduced alpha-synuclein accumulation and modulated microglial response in the brain of the transgenic mice including the elevated expression of arginase1 that marks M2 microglia. Thus, anthocyanin-rich wheat is suggested as a promising source of functional nutrition at the early stages of neurodegenerative disorders.

Effects of caloric restriction on retinal aging and neurodegeneration.

Glaucoma is the most common neurodegenerative cause of irreversible blindness worldwide. Restricted caloric regimens are an attractive approach for delaying the progression of neurodegenerative diseases. Here we review the current literature on the effects of caloric restriction on retinal neurons, under physiological and pathological conditions. We focused on autophagy as one of the mechanisms modulated by restricted caloric regimens and involved in the death of retinal ganglion cells (RGCs) over the course of glaucoma.

Brain glucose and ketone utilization in brain aging and neurodegenerative diseases.

To meet its high energy demands, the brain mostly utilizes glucose. However, the brain has evolved to exploit additional fuels, such as ketones, especially during prolonged fasting. With aging and neurodegenerative diseases (NDDs), the brain becomes inefficient at utilizing glucose due to changes in glia and neurons that involve glucose transport, glycolytic and Krebs cycle enzyme activities, and insulin signaling. Positron emission tomography and magnetic resonance spectroscopy studies have identified glucose metabolism abnormalities in aging, Alzheimer's disease (AD) and other NDDs in vivo. Despite glucose hypometabolism, brain cells can utilize ketones efficiently, thereby providing a rationale for the development of therapeutic ketogenic interventions in AD and other NDDs. This review compares available ketogenic interventions and discusses the potential of the potent oral Ketone Ester for future therapeutic use in AD and other NDDs characterized by inefficient glucose utilization.

Honey and obesity-related dysfunctions: a summary on health benefits.

Honey is a natural product, containing flavonoids and phenolic acids, appreciated for its therapeutic abilities since ancient times. Although the bioactive potential is linked to the composition, that is variable depending on mainly the botanical origin, honey has antioxidant and anti-inflammatory properties. Therefore, honey, administered alone or in combination with conventional therapy, might result useful in the management of chronic diseases that are commonly associated with oxidative stress and inflammation state. Obesity is a metabolic disorder characterized by visceral adiposity. The adipose tissue becomes hypertrophic and undergoes hyperplasia, resulting in a hypoxic environment, oxidative stress and production of pro-inflammatory mediators that can be responsible for other disorders, such as metabolic syndrome and neurodegeneration. Experimental evidence from animals have shown that honey improves glycemic control and lipid profile with consequent protection from endothelial dysfunction and neurodegeneration. The purpose of the present review is to summarize the current literature concerning the beneficial effects of honey in the management of the obesity-related dysfunctions, including neurodegeneration. Based on the key constituents of honey, the paper also highlights polyphenols to be potentially responsible for the health benefits of honey. Further well-designed and controlled studies are necessary to validate these benefits in humans.

The dichotomous role of the gut microbiome in exacerbating and ameliorating neurodegenerative disorders.

INTRODUCTION: Age related neurodegenerative disorders affect millions of people around the world. The role of the gut microbiome (GM) in neurodegenerative disorders has been elucidated over the past few years. Dysbiosis of the gut microbiome ultimately results in neurodegeneration. However, the gut microbiome can be modulated to promote neuro-resilience. AREAS COVERED: This review is focused on demonstrating the role of the gut microbiome in host physiology in Parkinson's disease (PD) and other neurodegenerative disorders. We will discuss how the microbiome will impact neurodegeneration in PD, Alzheimer's Disease (AD), Multiple sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), and finally discuss how the gut microbiome can be influenced through diet and lifestyle. EXPERT OPINION: Currently, much of the focus has been to study the mechanisms by which the microbiome induces neuroinflammation and neurodegeneration in PD, AD, MS, ALS. In particular, the role of certain dietary flavonoids in regulation of gut microbiome to promote neuro-resilience. Polyphenol prebiotics delivered in combination with probiotics (synbiotics) present an exciting new avenue to harness the microbiome to attenuate immune inflammatory responses which ultimately may influence brain cascades associated with promotion of neurodegeneration across the lifespan.

Olive Oil Polyphenols in Neurodegenerative Pathologies.

Neurodegenerative diseases lead to the death of nerve cells in the brain or the spinal cord. A wide range of diseases are included within the group of neurodegenerative disorders, with the most common ones being dementia, Alzheimer's, and Parkinson's diseases. Millions of older people are suffering from such pathologies. The global increase of life expectancy unavoidably leads to a consequent increase in the number of people who will be at some degree affected by neurodegenerative-related diseases. At this moment, there is no effective therapy or treatment that can reverse the loss of neurons. A growing number of studies highlight the value of the consumption of medical foods, and in particular olive oil, as one of the most important components of the Mediterranean diet. A diet based on extra virgin olive oil seems to contribute toward the lowering of risk of age-related pathologies due to high phenol concentration. The link of a polyphenol found in extra virgin olive oil, namely, tyrosol, with the protein tyrosinase, associated to Parkinson's disease is underlined as a paradigm of affiliation between polyphenols and neurodegenerative disorders.