A co jak nie ma HDAC? Bo zablokowane np. kurkuminÄ
?
Epigenetics:
There are various animal studies that suggest amphetamine produces a large portion of its sensitization via epigenetic changes primarily through CREB and histone deacetylase (HDAC) activity. However, if the mouse studies are to be applied to humans the picture becomes complicated. Co-administration of HDACI’s and amphetamine produces increased sensitization and conditioned place preference
http://onlinelibrary.wiley.com/doi/1...0.03321.x/fullCurcumin provides an interesting approach to this by inhibiting virtually every epigenetic mechanism under the sun, though the exact concentrations needed for significant inhibition of the various pathways in humans is still unknown at this point. CREB inhibition would stop the immediate-early response gene (IERG) activation and in turn long term epigenetic changes, while HDAC inhibition (a process downstream of CREB) would theoretically lead to an acute increase in sensitization and production of IERG proteins. Now during a “tolerance break” repeated HDACI application post amphetamine was shown to decrease sensitization which may be a relevant process in humans.
But, then there’s the possibility of histone acetyl transferase (HAT) playing a large role in the equation. Curcumin is a pretty bitching inhibitor of HAT, more so than HDAC in rats at least. This suggests that the potential negative effects of HDAC acutely on sensitization may not be an issue.
http://www.ncbi.nlm.nih.gov/pubmed/20383415But, going back to the IERG’s it appears that they also play a role in the NMDA antagonist mechanism of action via CREB
http://www.jneurosci.org/content/16/13/4231.short. And, curcumin appears to have a effect on NMDA calcium influx too
http://www.ncbi.nlm.nih.gov/pubmed/20015232.
So to sum it all up: curcumin is kind of like the sawn off shotgun of epigenetic modulators, showing promise on several fronts but with its 9/21 positive response rate we’d need better controlled anecdotal or actual clinical trials to make more sense out of it. Also, there may be glaring species differences with the various proteins curcumin binds between humans and rats/mice that I’m too lazy to check out (hint hint). Also, don’t be afraid of trialling more selective inhibitors of epigenetic mechanisms as long as you’re smart and methodical about it.
http://www.ncbi.nlm.nih.gov/pubmed/21466474BaĹdzo ciekawa ta epigenetyka. Dalsze badania sÄ
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