Editing Resveratrol

[[Information on nutritional supplements people with ALS have been taking]]

* [https://en.wikipedia.org/wiki/Resveratrol Wikipedia page]
* [http://www.medicalnewstoday.com/articles/241120.php Medical News Today]

== 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. {{#pmid:21983205|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.'' {{#pmid:17927823|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.'' {{#pmid:17581637|kim2007}}

Resveratrol specifically '''inhibits the TRIF pathway in TLR3 and TLR4 signaling''', by targetting TBK1 and RIP1 in the TRIF complex. {{#pmid:16116226|youn2005}}

''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'''.''{{#pmid:16322078|kutuk2006}} 

''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.'' {{#pmid:17086191|baur2006}}

[http://www.resveratrolnews.com/how-modern-medicine-obfuscates-resveratrol-science/833/ Resveratrol News]: Collection of sources suggesting that low dosing (up to about 150 mg/day) is beneficial but high doses harmful.

== Research article link collection ==

[http://alsanesthetics.org/research/solving-the-puzzle/potential-therapeutics-foci-of-intervention/117-resveratrol Research papers on resveratrol and ALS]

== Discussion threads on the ALSTDI forum ==

* [http://www.alstdi.org/forum/yaf_postst53763_resveratrol-delays-wallerian-degeneration-in-a-nad-and-dbc1-dependent-manner.aspx Resveratrol delays Wallerian degeneration in a NAD+ and DBC1 dependent manner] (especially [http://www.als.net/forum/yaf_postsm384855_Resveratrol-delays-Wallerian-degeneration-in-a-NAD-and-DBC1-dependent-manner.aspx#384855 this post])
* [http://www.alstdi.org/forum/yaf_postst53900_quality-control-of-mitochondria-in-neurons.aspx Quality control of mitochondria in neurons]: ''resveratrol and leucine or HMB, combined, yielded Sirt1 and Sirt3 activity increases in the ~50% range (p < 0.05) and AMPK increases of +42% and +55% (p < 0.03); particularly noteworthy are the ~125-175% increases (p < 0.02) muscle cells (remember: Sirt3 is expressed in the mitochondria!)''

== References ==
 

[[Category:Supplement data pages]]