Neuroprotective Mechanisms of Resveratrol in Alzheimer's Disease: Role of SIRT1 (original) (raw)
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Current Neurovascular Research, 2009
One of the current problems in medicine research is the development of safe drugs for the treatment of neurological disorders. Furthermore, there is a close relationship between the process of aging and the appearance of neurological disorders, particularly Parkinson's disease and Alzheimer's disease. Therefore, an ideal compound would have two characteristics: neuroprotective action and an anti-aging effect. The natural compound resveratrol is a suitable candidate for this purpose due to its low toxicity and antioxidant properties. In addition, recent research has shown that it has an anti-aging effect in rat, yeast, Caenorhabditis elegans, and Drosophila, although the mechanism involved in this process remains to be clarified. One hypothesis is that by activating Sirtuin 1, resveratrol modulates the activity of numerous proteins, including peroxisome proliferator-activated receptor coactivator-1 (PGC-1 alpha), the FOXO family, Akt (protein kinase B) and nuclear factor-(NF ). This review summarises recent research on the molecular mechanisms through which resveratrol might exert its therapeutic effects via the interaction with Sirtuin 1, as well as other targets. In addition, we discuss the possibility of using resveratrol in the treatment of neurodegenerative diseases.
Neuroprotective role of trans-resveratrol in a murine model of familial Alzheimer's disease
Journal of Alzheimer's disease : JAD, 2014
The amyloid-β protein precursor/presenilin 1 (AβPP/PS1) mouse model of Alzheimer's disease (AD) has provided robust neuropathological hallmarks of familial AD-like pattern. AD is a neurodegenerative process that causes severe cognitive impairment; it is characterized by the accumulation of amyloid-β (Aβ) and hyperphosphorylated tau forms and by oxidative and inflammatory processes in brain. Currently, efforts are made to understand biochemical pathways because there is no effective therapy for AD. Resveratrol is a polyphenol that induces expression and activation of several neuroprotective pathways involving Sirtuin1 and AMPK. The objective of this work was to assess the effect of oral resveratrol administration on AβPP/PS1 mice. Long-term resveratrol treatment significantly prevented memory loss as measured by the object recognition test. Moreover, resveratrol reduced the amyloid burden and increased mitochondrial complex IV protein levels in mouse brain. These protective effec...
Molecular Neurobiology
Resveratrol is a natural compound that mimics the antioxidant and antiaging effects of caloric restriction, mainly mediated through SIRT1, a deacetylase that induces longevity and neuroprotection. We aimed to analyze the effects of resveratrol on the brain status of control non-transgenic (NoTg) and AD transgenic (3xTg-AD) mice to discern the mechanisms involved in a potential inducement of resilience against age-related neurodegeneration and Alzheimer's disease (AD). Mice were fed with a diet supplemented with 100 mg/kg of trans-resveratrol from 2 months of age during 10 months. Resveratrol administration induced complete protection against memory loss and brain pathology in 3xTg-AD mice, and also induced cognitive enhancement in healthy NoTg mice. Resveratrol improved exploration and reduced anxiety in both mouse strains, indicative of well-being. Resveratrol reduced the presence of Aβ and p-tau pathology in the hippocampus of the 3xTg-AD mouse. Proteostasis analysis showed the following in both NoTg and 3xTg-AD mice: (i) increased levels of the amyloid degrading enzyme neprilysin; (ii) reduction of the amyloidogenic secretase BACE1, and (iii) increase of proteasome protein levels and enhancement of proteasome activity. Resveratrol also increased AMPK protein levels, then upregulating the SIRT1 pathway, as shown by the activation of PGC-1α and CREB in both mice, resulting in further beneficial changes. Our data demonstrated that resveratrol induces cognitive enhancement and neuroprotection against amyloid and tau pathologies. Improvement of proteostasis by resveratrol, in both healthy and AD mice, suggests that it is a mechanism of brain resilience and defense against neurodegeneration caused by the accumulation of aberrant proteins.
Biophysical interaction of resveratrol with sirtuin pathway: Significance in Alzheimer's disease
Frontiers in bioscience (Landmark edition), 2018
Alzheimer disease (AD) is a widespread neurodegenerative condition that leads to progressive cognitive dysfunction in elderly population. Despite several attempts aimed at molecular determinants of AD, effective disease modifying treatment options are highly limited. Recently, use of natural supplements has gained considerable attention in AD research due to their cost effective and long lasting health beneficial properties. Resveratrol (RSV) is a naturally occurring polyphenolic compound found majorly in grapes. RSV has been shown to exert a plethora of medical benefits due to its anti-oxidant, anti-aging, anti-inflammatory, anti-malignant and neuroprotective properties. In particular, RSV has been shown to increase memory performance. The neuroprotective effect of RSV has strongly been linked to the depolymerization of amyloid β fibrils. However, the molecular targets of RSV remain the subject of investigation. This review was aimed to comprehend the existing knowledge on the neur...
Neuroprotective effects of resveratrol in Alzheimer disease pathology
Frontiers in Aging Neuroscience, 2014
Alzheimer's disease is a chronic neurodegenerative disorder characterized by a progressive loss of cognitive and behavioral abilities. Extracellular senile plaques and intracellular neurofibrillary tangles are hallmarks of AD. Researchers aim to analyze the molecular mechanisms underlying AD pathogenesis; however, the therapeutic options available to treat this disease are inadequate. In the past few years, several studies have reported interesting insights about the neuroprotective properties of the polyphenolic compound resveratrol (3, 5, 4 -trihydroxy-trans-stilbene) when used with in vitro and in vivo models of AD. The aim of this review is to focus on the neuroprotective and antioxidant effects of resveratrol on AD and its multiple potential mechanisms of action. In addition, because the naturally occurring forms of resveratrol have a very limited half-life in plasma, a description of potential analogs aimed at increasing the bioavailability in plasma is also discussed.
Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer's disease
Background: Treatment of mild-moderate Alzheimer's disease (AD) subjects (N = 119) for 52 weeks with the SIRT1 activator resveratrol (up to 1 g by mouth twice daily) attenuates progressive declines in CSF Aβ40 levels and activities of daily living (ADL) scores. Methods: For this retrospective study, we examined banked CSF and plasma samples from a subset of AD subjects with CSF Aβ42 <600 ng/ml (biomarker-confirmed AD) at baseline (N = 19 resveratrol-treated and N = 19 placebo-treated). We utilized multiplex Xmap technology to measure markers of neurodegenerative disease and metalloproteinases (MMPs) in parallel in CSF and plasma samples.
Effects of Resveratrol and Other Polyphenols on Sirt1: Relevance to Brain Function During Aging
Current Neuropharmacology
Background: Classically the oxidative stress and more recently inflammatory processes have been identified as the major causes of brain aging. Oxidative stress and inflammation affect each other, but there is more information about the effects of oxidative stress on aging than regarding the contribution of inflammation on it. Methods: In the intense research for methods to delay or mitigate the effects of aging, are interesting polyphenols, natural molecules synthesized by plants (e.g. resveratrol). Their antioxidant and anti-inflammatory properties make them useful molecules in the prevention of aging. Results: The antiaging effects of polyphenols could be due to several related mechanisms, among which are the prevention of oxidative stress, SIRT1 activation and inflammaging modulation, via regulation of some signaling pathways, such as NF-κB. Conclusion: In this review, we describe the positive effects of polyphenols on the prevention of the changes that occur during aging in the brain and their consequences on cognition, emphasizing the possible modulation of inflammaging by polyphenols through a SIRT1-mediated mechanism.
Resveratrol and Neuroprotection: Impact and Its Therapeutic Potential in Alzheimer's Disease
Frontiers in Pharmacology
Alzheimer’s disease (AD) is a progressive cortex and hippocampal neurodegenerative disease which ultimately causes cognitively impaired decline in patients. The AD pathogen is a very complex process, including aggregation of Aβ (β-amyloid peptides), phosphorylation of tau-proteins, and chronic inflammation. Exactly, resveratrol, a polyphenol present in red wine, and many plants are indicated to show the neuroprotective effect on mechanisms mostly above. Resveratrol plays an important role in promotion of non-amyloidogenic cleavage of the amyloid precursor protein. It also enhances the clearance of amyloid beta-peptides and reduces the damage of neurons. Most experimental research on AD and resveratrol has been performed in many species, both in vitro and in vivo, during the last few years. Nevertheless, resveratrol’s effects are restricted by its bioavailability in the reservoir. Therefore, scientists have tried to improve its efficiency by using different methods. This review focus...
Resveratrol in Alzheimer's disease: a review of pathophysiology and therapeutic potential
Arquivos de Neuro-Psiquiatria, 2020
Background: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive and irreversible loss of cognitive function. The presence of senile plaques is one of the pathological markers of the disease and is associated with the onset of neuroinflammatory mechanisms. The exact pathophysiology of AD has not been completely understood, and there are no curative therapies yet. Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a polyphenol that is noted for its antioxidant and anti-inflammatory properties. Objective: To review the role of resveratrol in the pathophysiological aspects of AD. Methods: This study carried out a literature review using PubMed/Medline, Virtual Health Library (VHL), Web of Sciences, SCOPUS and the Cochrane Library databases. Original research articles, describing both in vitro and in vivo experiments, published between 2008 and 2018, were included. Results: We identified 667 articles, of which 619 were excluded because they were repea...
Resveratrol as a Therapeutic Agent for Neurodegenerative Diseases
Molecular Neurobiology, 2010
Excess production of reactive oxygen species in the brain has been implicated as a common underlying risk factor for the pathogenesis of a number of neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. In recent years, there is considerable interest concerning investigation of antioxidative and anti-inflammatory effects of phenolic compounds from different botanical sources. In this review, we first describe oxidative mechanisms associated with stroke, AD, and PD, and subsequently, we place emphasis on recent studies implicating neuroprotective effects of resveratrol, a polyphenolic compound derived from grapes and red wine. These studies show that the beneficial effects of resveratrol are not only limited to its antioxidant and anti-inflammatory action but also include activation of sirtuin 1 (SIRT1) and vitagenes, which can prevent the deleterious effects triggered by oxidative stress. In fact, SIRT1 activation by resveratrol is gaining importance in the development of innovative treatment strategies for stroke and other neurodegenerative disorders. The goal here is to provide a better understanding of the mode of action of resveratrol and its possible use as a potential therapeutic agent to ameliorate stroke damage as well as other age-related neurodegenerative disorders.