Resveratrol

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Information on nutritional supplements people with ALS have been taking

Effects on ALS

In rat brain cortical motoneuron primary culture, resveratrol protects against neurotoxic effects and antagonizes the [Ca(+2)](c) elevation produced by ALS/CSF. However, riluzole does not afford protection and antagonizes the resveratrol-elicited neuroprotective effects. {{#pmidː21983205|yanez2011}}

Our results indicate that resveratrol potently reduced LPS-induced PGE2 synthesis and the formation of 8-iso-PGF2 alpha, a measure of free radical production. Interestingly, resveratrol dose-dependently reduced the expression (mRNA and protein) of mPGES-1, which is a key enzyme responsible for the synthesis of PGE2 by activated microglia, whereas resveratrol did not affect the expression of COX-2. Resveratrol is therefore the first known inhibitor which specifically prevents mPGES-1 expression without affecting COX-2 levels. Another important observation of the present study is that other COX-1 selective inhibitors (SC-560 and Valeroyl Salicylate) potently reduced PGE2 and 8-iso-PGF2 alpha production by LPS-activated microglia. These findings suggest that the naturally occurring polyphenol resveratrol is able to reduce microglial activation, an effect that might help to explain its neuroprotective effects in several in vivo models of brain injury. {{#pmidː17927823|candelario2007}}

Here, we report that a human homologue of SIR2, SIRT1, is upregulated in mouse models for AD, ALS and in primary neurons challenged with neurotoxic insults. In cell-based models for AD/tauopathies and ALS, SIRT1 and resveratrol, a SIRT1-activating molecule, both promote neuronal survival. In the inducible p25 transgenic mouse, a model of AD and tauopathies, resveratrol reduced neurodegeneration in the hippocampus, prevented learning impairment, and decreased the acetylation of the known SIRT1 substrates PGC-1alpha and p53. [3]

Resveratrol specifically inhibits the TRIF pathway in TLR3 and TLR4 signaling, by targetting TBK1 and RIP1 in the TRIF complex. [4]

Resveratrol effectively prevented HNE-induced JNK and caspase activation, and hence apoptosis. Activation of AP-1 along with increased c-Jun and phospho-c-Jun levels could be inhibited by pretreatment of cells with resveratrol. Moreover, Nrf2 downregulation by HNE could also be blocked by resveratrol.[5]

Resveratrol produces changes associated with longer lifespan, including increased insulin sensitivity, reduced insulin-like growth factor-1 (IGF-I) levels, increased AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) activity, increased mitochondrial number, and improved motor function. Parametric analysis of gene set enrichment revealed that resveratrol opposed the effects of the high-calorie diet in 144 out of 153 significantly altered pathways. [6]

Research article link collection

Research papers on resveratrol and ALS

Discussion threads on the ALSTDI forum

References

[3] <bibtex> @article{Kim2007, abstract = {A progressive loss of neurons with age underlies a variety of debilitating neurological disorders, including Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), yet few effective treatments are currently available. The SIR2 gene promotes longevity in a variety of organisms and may underlie the health benefits of caloric restriction, a diet that delays aging and neurodegeneration in mammals. Here, we report that a human homologue of SIR2, SIRT1, is upregulated in mouse models for AD, ALS and in primary neurons challenged with neurotoxic insults. In cell-based models for AD/tauopathies and ALS, SIRT1 and resveratrol, a SIRT1-activating molecule, both promote neuronal survival. In the inducible p25 transgenic mouse, a model of AD and tauopathies, resveratrol reduced neurodegeneration in the hippocampus, prevented learning impairment, and decreased the acetylation of the known SIRT1 substrates PGC-1alpha and p53. Furthermore, injection of SIRT1 lentivirus in the hippocampus of p25 transgenic mice conferred significant protection against neurodegeneration. Thus, SIRT1 constitutes a unique molecular link between aging and human neurodegenerative disorders and provides a promising avenue for therapeutic intervention.}, author = {Kim, Dohoon and Nguyen, Minh Dang and Dobbin, Matthew M and Fischer, Andre and Sananbenesi, Farahnaz and Rodgers, Joseph T and Delalle, Ivana and Baur, Joseph A and Sui, Guangchao and Armour, Sean M and Puigserver, Pere and Sinclair, David A and Tsai, Li-Huei}, doi = {10.1038/sj.emboj.7601758}, issn = {0261-4189}, journal = {The EMBO Journal}, keywords = {Acetylation,Acetylation: drug effects,Alzheimer Disease,Alzheimer Disease: genetics,Alzheimer Disease: metabolism,Alzheimer Disease: pathology,Amyotrophic Lateral Sclerosis,Amyotrophic Lateral Sclerosis: genetics,Amyotrophic Lateral Sclerosis: metabolism,Amyotrophic Lateral Sclerosis: pathology,Animals,Cells, Cultured,Cyclin-Dependent Kinase 5,Cyclin-Dependent Kinase 5: metabolism,Disease Models, Animal,Enzyme Activation,Gene Expression Regulation,Humans,Mice,Mice, Transgenic,Mutation,Mutation: genetics,Nerve Degeneration,Nerve Degeneration: genetics,Nerve Degeneration: metabolism,Nerve Degeneration: pathology,Rats,Sirtuin 1,Sirtuins,Sirtuins: genetics,Sirtuins: metabolism,Stilbenes,Stilbenes: pharmacology,Superoxide Dismutase,Superoxide Dismutase: genetics,Superoxide Dismutase: metabolism,Tumor Suppressor Protein p53,Tumor Suppressor Protein p53: metabolism}, mendeley-groups = {resveratrol}, month = jun, number = {13}, pages = {3169--3179}, pmid = {17581637}, title = Template:SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis, url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1914106\&tool=pmcentrez\&rendertype=abstract}, volume = {26}, year = {2007} } </bibtex>

[4] <bibtex> @article{Youn2007, abstract = {Toll-like receptors (TLRs) induce innate immune responses that are essential for host defenses against invading microbial pathogens, thus leading to the activation of adaptive immune responses. In general, TLRs have two major downstream signaling pathways: the MyD88- and TRIF-dependent pathways, which lead to the activation of and IRF3. Numerous studies have demonstrated that certain phytochemicals possessing anti-inflammatory effects inhibit activation induced by pro-inflammatory stimuli, including lipopolysaccharides and . However, the direct molecular targets for such anti-inflammatory phytochemicals have not been fully identified. Identifying the direct targets of phytochemicals within the TLR pathways is important because the activation of TLRs by pro-inflammatory stimuli can induce inflammatory responses that are the key etiological conditions in the development of many chronic inflammatory diseases. In this paper we discuss the molecular targets of resveratrol, (-)-epigallocatechin-3-gallate (EGCG), and curcumin in the TLR signaling pathways. Resveratrol specifically inhibited the TRIF pathway in TLR3 and TLR4 signaling, by targetting TBK1 and RIP1 in the TRIF complex. Furthermore, EGCG suppressed the activation of IRF3 by targetting TBK1 in the TRIF-dependent signaling pathways. In contrast, the molecular target of curcumin within the TLR signaling pathways is the receptor itself, in addition to . Together, certain dietary phytochemicals can modulate TLR-derived signaling and inflammatory target gene expression, and in turn, alter susceptibility to microbial infection and chronic inflammatory diseases. Anti-inflammatory Effects of Resveratrol, (-)-Epigallocatechin-3-gallate and Curcumin by the Modulation of Toll-like Receptor Signaling Pathways - ResearchGate. Available from: http://www.researchgate.net/publication/264185041\_Anti-inflammatory\_Effects\_of\_Resveratrol\_(-)-Epigallocatechin-3-gallate\_and\_Curcumin\_by\_the\_Modulation\_of\_Toll-like\_Receptor\_Signaling\_Pathways [accessed Nov 6, 2015].}, author = {Youn, Hyung-Sun}, issn = {0367-6293}, journal = {Korean Journal of Food Science and Technology}, mendeley-groups = {resveratrol}, month = jan, number = {5}, title = Template:Anti-inflammatory Effects of Resveratrol, (-)-Epigallocatechin-3-gallate and Curcumin by the Modulation of Toll-like Receptor Signaling Pathways, url = {http://www.researchgate.net/publication/264185041\_Anti-inflammatory\_Effects\_of\_Resveratrol\_(-)-Epigallocatechin-3-gallate\_and\_Curcumin\_by\_the\_Modulation\_of\_Toll-like\_Receptor\_Signaling\_Pathways}, volume = {39}, year = {2007} } </bibtex>

[5] <bibtex> @article{Kutuk2006, abstract = {In the present study we have studied the effect of resveratrol in signal transduction mechanisms leading to apoptosis in 3T3 fibroblasts when exposed to 4-hydroxynonenal (HNE). In order to gain insight into the mechanisms of apoptotic response by HNE, we followed MAP kinase and caspase activation pathways; HNE induced early activation of JNK and p38 proteins but downregulated the basal activity of ERK (1/2). We were also able to demonstrate HNE-induced release of cytochrome c from mitochondria, caspase-9, and caspase-3 activation. Resveratrol effectively prevented HNE-induced JNK and caspase activation, and hence apoptosis. Activation of AP-1 along with increased c-Jun and phospho-c-Jun levels could be inhibited by pretreatment of cells with resveratrol. Moreover, Nrf2 downregulation by HNE could also be blocked by resveratrol. Overexpression of dominant negative c-Jun and JNK1 in 3T3 fibroblasts prevented HNE-induced apoptosis, which indicates a role for JNK-c-Jun/AP-1 pathway. In light of the JNK-dependent induction of c-Jun/AP-1 activation and the protective role of resveratrol, these data may show a critical potential role for JNK in the cellular response against toxic products of lipid peroxidation. In this respect, resveratrol acting through MAP kinase pathways and specifically on JNK could have a role other than acting as an antioxidant-quenching reactive oxygen intermediate.}, author = {Kutuk, Ozgur and Poli, Giuseppe and Basaga, Huveyda}, doi = {10.1093/toxsci/kfj055}, issn = {1096-6080}, journal = {Toxicological sciences : an official journal of the Society of Toxicology}, keywords = {Aldehydes,Aldehydes: toxicity,Animals,Antioxidants,Antioxidants: pharmacology,Apoptosis,Apoptosis: drug effects,Caspase 3,Caspase 9,Caspases,Caspases: biosynthesis,Cytochromes c,Cytochromes c: metabolism,Dose-Response Relationship, Drug,Drug Antagonism,Fibroblasts,Fibroblasts: drug effects,Fibroblasts: metabolism,Fibroblasts: pathology,JNK Mitogen-Activated Protein Kinases,JNK Mitogen-Activated Protein Kinases: metabolism,MAP Kinase Kinase 4,MAP Kinase Kinase 4: metabolism,Mice,Mitochondria,Mitochondria: drug effects,Mitochondria: enzymology,Signal Transduction,Signal Transduction: drug effects,Stilbenes,Stilbenes: pharmacology,Swiss 3T3 Cells,Transcription Factor AP-1,Transcription Factor AP-1: metabolism}, mendeley-groups = {resveratrol}, month = mar, number = {1}, pages = {120--32}, pmid = {16322078}, title = Template:Resveratrol protects against 4-hydroxynonenal-induced apoptosis by blocking JNK and c-JUN/AP-1 signaling., url = {http://www.ncbi.nlm.nih.gov/pubmed/16322078}, volume = {90}, year = {2006} } </bibtex>

[6] <bibtex> @article{Baur2006, abstract = {Resveratrol (3,5,4'-trihydroxystilbene) extends the lifespan of diverse species including Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. In these organisms, lifespan extension is dependent on Sir2, a conserved deacetylase proposed to underlie the beneficial effects of caloric restriction. Here we show that resveratrol shifts the physiology of middle-aged mice on a high-calorie diet towards that of mice on a standard diet and significantly increases their survival. Resveratrol produces changes associated with longer lifespan, including increased insulin sensitivity, reduced insulin-like growth factor-1 (IGF-I) levels, increased AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-gamma coactivator 1$\alpha$ (PGC-1$\alpha$) activity, increased mitochondrial number, and improved motor function. Parametric analysis of gene set enrichment revealed that resveratrol opposed the effects of the high-calorie diet in 144 out of 153 significantly altered pathways. These data show that improving general health in mammals using small molecules is an attainable goal, and point to new approaches for treating obesity-related disorders and diseases of ageing.}, author = {Baur, J.A. and Pearson, K.J. and Price, N.L. and Jamieson, H.A. and Lerin, C. and Kalra, A. and Prabhu, V.V. and Allard, J.S. and Lopez-Lluch, G. and Lewis, K.}, issn = {0028-0836}, journal = {Nature}, keywords = {food intake,gene expression regulation,health status,high energy diet,longevity,metabolism,mice,mortality,oral administration,resveratrol}, language = {English}, mendeley-groups = {resveratrol}, title = Template:Resveratrol improves health and survival of mice on a high-calorie diet, url = {http://agris.fao.org/agris-search/search.do?recordID=US201300758937}, year = {2006} } </bibtex>