Resveratrol protects dopaminergic neurons in midbrain slice culture

[olsen]

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]

[lori86]

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]

[Sasha]

"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]"

[ZucchiniFlower]

A good article:

http://www.lef.org/magazine/mag2007/mar2007_report_resveratrol_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/releases/062107kazantsev.html

research article:

http://www.sciencemag.org/cgi/rapidpdf/1143780.pdf