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Putative Role of Red Wine Polyphenols against Brain Pathology in Alzheimer's and Parkinson's Disease.

ABSTRACT: Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common age-related neurodegenerative disorders and hence pose remarkable socio-economical burdens to both families and state. Although AD and PD have different clinical and neuropathological features, they share common molecular mechanisms that appear to be triggered by multi-factorial events, such as protein aggregation, mitochondrial dysfunction, oxidative stress (OS), and neuroinflammation, ultimately leading to neuronal cell death. Currently, there are no established and validated disease-modifying strategies for either AD or PD. Among the various lifestyle factors that may prevent or slow age-related neurodegenerative diseases, epidemiological studies on moderate consumption of red wine, especially as part of a holistic Mediterranean diet, have attracted increasing interest. Red wine is particularly rich in specific polyphenolic compounds that appear to affect the biological processes of AD and PD, such as quercetin, myricetin, catechins, tannins, anthocyanidins, resveratrol, and ferulic acid. Indeed, there is now a consistent body of in vitro and in vivo data on the neuroprotective effects of red wine polyphenols (RWP) showing that they do not merely possess antioxidant properties, but may additionally act upon, in a multi-target manner, the underlying key mechanisms featuring in both AD and PD. Furthermore, it is important that bioavailability issues are addressed in order for neuroprotection to be relevant in a clinical study scenario. This review summarizes the current knowledge about the major classes of RWP and places into perspective their potential to be considered as nutraceuticals to target neuropathology in AD and PD.

SUBMITTER: Caruana M

PROVIDER: S-EPMC4981604 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Putative Role of Red Wine Polyphenols against Brain Pathology in Alzheimer's and Parkinson's Disease.

Caruana Mario M Cauchi Ruben R Vassallo Neville N

Frontiers in nutrition 20160812

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common age-related neurodegenerative disorders and hence pose remarkable socio-economical burdens to both families and state. Although AD and PD have different clinical and neuropathological features, they share common molecular mechanisms that appear to be triggered by multi-factorial events, such as protein aggregation, mitochondrial dysfunction, oxidative stress (OS), and neuroinflammation, ultimately leading to neuronal cell ...[more]

PMID: 27570766

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Project description:BackgroundA greater reduction in cardiovascular risk and vascular protection associated with diet rich in polyphenols are generally accepted; however, the molecular targets for polyphenols effects remain unknown. Meanwhile evidences in the literature have enlightened, not only structural similarities between estrogens and polyphenols known as phytoestrogens, but also in their vascular effects. We hypothesized that alpha isoform of estrogen receptor (ERalpha) could be involved in the transduction of the vascular benefits of polyphenols.Methodology/principal findingsHere, we used ERalpha deficient mice to show that endothelium-dependent vasorelaxation induced either by red wine polyphenol extract, Provinols, or delphinidin, an anthocyanin that possesses similar pharmacological profile, is mediated by ERalpha. Indeed, Provinols, delphinidin and ERalpha agonists, 17-beta-estradiol and PPT, are able to induce endothelial vasodilatation in aorta from ERalpha Wild-Type but not from Knock-Out mice, by activation of nitric oxide (NO) pathway in endothelial cells. Besides, silencing the effects of ERalpha completely prevented the effects of Provinols and delphinidin to activate NO pathway (Src, ERK 1/2, eNOS, caveolin-1) leading to NO production. Furthermore, direct interaction between delphinidin and ERalpha activator site is demonstrated using both binding assay and docking. Most interestingly, the ability of short term oral administration of Provinols to decrease response to serotonin and to enhance sensitivity of the endothelium-dependent relaxation to acetylcholine, associated with concomitant increased NO production and decreased superoxide anions, was completely blunted in ERalpha deficient mice.Conclusions/significanceThis study provides evidence that red wine polyphenols, especially delphinidin, exert their endothelial benefits via ERalpha activation. It is a major breakthrough bringing new insights of the potential therapeutic of polyphenols against cardiovascular pathologies.

Project description:Parkinson's disease is delayed in clinical onset, asymmetric in initial appearance, and slow in progression. One explanation for these characteristics may be a boost in natural defenses after early exposure to mild cellular stress. As the patient ages and resilience recedes, however, stress levels may become sufficiently high that toxic cellular responses can no longer be curbed, culminating in inverted U-shaped stress-response curves as a function of disease duration. If dopaminergic systems are indeed capable of responding to mild stress with effective natural defenses, experimental models of Parkinson's disease should adhere to the principles of preconditioning, whereby stress exposure fortifies cells and tempers the toxic sequelae of subsequent stressors. Here, I review evidence favoring the efficacy of preconditioning in dopaminergic systems. Recent animal work also raises the possibility that cross-hemispheric preconditioning may arrest the spread of asymmetric Parkinson's pathology to the other side of the brain. Indeed, compensatory homeostatic systems have long been hypothesized to maintain neurological function until a threshold of cell loss is exceeded and are often displayed as inverted U-shaped curves. However, some stress responses assume an exponential or sigmoidal profile as a function of disease severity, suggesting end-stage deceleration of disease processes. Thus, surviving dopaminergic neurons may become progressively harder to kill, with the dorsal nigral tier dying slower due to superior baseline defenses, inducible conditioning capacity, or delayed dorsomedial nigral spread of disease. In addition, compensatory processes may be useful as biomarkers to distinguish "responder patients" from "nonresponders" before clinical trials. However, another possibility is that defenses are already maximally conditioned in most patients and no further boost is possible. A third alternative is that genuinely diseased human cells cannot be conditioned, in contrast to preclinical models, none of which faithfully recapitulate age-related human conditions. Disease-related "conditioning deficiencies" would then explain how Parkinson's pathology takes root, progressively shrinks defenses, and eventually kills the patient.

Dataset Information

Putative Role of Red Wine Polyphenols against Brain Pathology in Alzheimer's and Parkinson's Disease.

Publications

Putative Role of Red Wine Polyphenols against Brain Pathology in Alzheimer's and Parkinson's Disease.

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