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06-24-2007, 09:21 AM | #1 | |||
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Biochem Pharmacol. 2007 Feb 15;73(4):550-60. Epub 2006 Nov 9.
Resveratrol protects dopaminergic neurons in midbrain slice culture from multiple insults. Okawara M, Katsuki H, Kurimoto E, Shibata H, Kume T, Akaike A. Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan. Increasing lines of evidence show that resveratrol, a polyphenol compound contained in several dietary products, exhibits cytoprotective actions. Notably, resveratrol activates sirtuin family of NAD-dependent histone deacetylases implicated in regulation of various cellular processes including gene transcription, DNA repair and apoptosis. Here we examined neuroprotective effect of resveratrol on dopaminergic neurons in organotypic midbrain slice culture. Resveratrol and quercetin, another sirtuin-activating polyphenol, prevented the decrease of dopaminergic neurons and the increase of propidium iodide uptake into slices induced by a dopaminergic neurotoxin 1-methyl-4-phenyl pyridinium (MPP(+)). Resveratrol also provided concentration-dependent neuroprotective effects against sodium azide, a mitochondrial complex IV inhibitor, and thrombin (EC number 3.4.21.5), a microglia-activating agent. Sirtuin inhibitors such as nicotinamide and sirtinol did not attenuate the protective effect of resveratrol against MPP(+) cytotoxicity. Instead, we found that resveratrol prevented accumulation of reactive oxygen species, depletion of cellular glutathione, and cellular oxidative damage induced by MPP(+), suggesting involvement of antioxidative properties in the neuroprotective action of resveratrol. On the other hand, resveratrol as well as a sirtuin activator NAD inhibited dopaminergic neurotoxicity of a DNA alkylating agent, N-methyl-N'-nitro-N- nitrosoguanidine (MNNG). Moreover, MNNG-induced increase in acetylation of p53, a representative target of sirtuin deacetylase activity, was suppressed by resveratrol. These results indicate that resveratrol can exert neuroprotective actions in dopaminergic neurons. Either antioxidative activity or sirtuin-activating potential may play an important role in the neuroprotectice actions of resveratrol against different kinds of insults. PMID: 17147953 [PubMed - indexed for MEDLINE]
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06-24-2007, 09:25 AM | #2 | ||
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something I have been looking into relates to the previous post:
Mol Aspects Med. 2007 Feb 16; [Epub ahead of print] SIRT1 and neuronal diseases. Tang BL, Chua CE. Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, Singapore 117597, Singapore. SIRT1 is the mammalian homologue of yeast silent information regulator (Sir)-2, a member of the sirtuin family of protein deacetylases which have gained much attention as mediators of lifespan extension in several model organisms. Induction of SIRT1 expression also attenuates neuronal degeneration and death in animal models of Alzheimer's disease and Huntington's disease. SIRT1 induction, either by sirtuin activators such as resveratrol, or metabolic conditioning associated with caloric restriction (CR), could be neuroprotective in several ways. It could promote the non-amyloidogenic cleavage of the amyloid precursor protein, enhance clearance of amyloid beta-peptides, and reduced neuronal damage through potential inhibition of neuroinflammatory signaling pathways. In addition, increased SIRT1 activity could alter neuronal transcription profiles to enhance anti- stress and anti-apoptotic gene activities, and has been proposed to underlie the inhibition of axonal degeneration in the Wallerian degeneration slow (Wld(s)) phenotype. As neuronal degeneration is a major pathophysiological aspect of human aging, understanding the mechanism of SIRT1 neuroprotection promises novel strategies in clinical intervention of neurodegenerative diseases. PMID: 17397914 [PubMed - as supplied by publisher] |
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06-25-2007, 09:25 PM | #3 | ||
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"Resveratrol
From Wikipedia, the free encyclopedia Jump to: navigation, search Resveratrol Resveratrol is a phytoalexin produced by several plants. It has also been produced by chemical synthesis.[1] Resveratrol is sold as a nutritional supplement. A number of beneficial health effects, such as anti-cancer, antiviral, neuroprotective, anti-aging, anti-inflammatory and life-prolonging effects have been reported, although these studies used animal subjects (e.g. rats). Resveratrol is found in the skin of red grapes and as a constituent of red wine but, based on extrapolation from animal trials, apparently not in sufficient amounts to explain the “French paradox” that the incidence of coronary heart disease is relatively low in southern France despite high dietary intake of saturated fats.[2] David Sinclair of the Harvard Medical School, and cofounder of Sirtris Pharmaceuticals,[3] has found that resveratrol increases the activity of a protein called SIRT1. Resveratrol significantly increases the lifespan of yeast and mice. There is hope that it could do the same for humans.[4]" |
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06-27-2007, 08:42 PM | #4 | |||
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A good article:
http://www.lef.org/magazine/mag2007/...eratrol_01.htm AND: Study identifies novel Parkinson's disease drug target Blocking enzyme activity may also reduce brain cell death in Huntington's, other disorders BOSTON - June 21, 2007 - Researchers at the MassGeneral Institute for Neurodegenerative Disease (MGH-MIND) have identified a potential new drug target for the treatment of Parkinson's disease and possibly for other degenerative neurological disorders. In an upcoming issue of the journal Science, the investigators describe finding, in cellular and animal models, that blocking the action of an enzyme called SIRT2 can protect the neurons damaged in Parkinson's disease from the toxic effects of alpha-synuclein, a protein that accumulates in the brains of Parkinson's patients. The study, which also suggests that inhibiting this pathway could help in the treatment of other conditions in which abnormal proteins accumulate in the brain, is receiving early online release on the Science Express website. "We have discovered a compelling new therapeutic approach for Parkinson's disease, which we expect will allow our scientists - as well as those at pharmaceutical and biotech companies - to pursue innovative new drugs that will treat and perhaps even cure this disorder," says Aleksey Kazantsev, PhD, director of MGH-MIND Drug Discovery Laboratory, who led the Science study. "Since the same sort of aggregation of misfolded proteins has been reported in Huntington's and Alzheimer's diseases - as well as Lewy body dementia, which also involves alpha-synuclein deposits - we plan to test this approach in those conditions as well......." article: http://www.massgeneral.org/news/rele...kazantsev.html research article: http://www.sciencemag.org/cgi/rapidpdf/1143780.pdf |
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