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Resveratrol and analogs inhibit amyloid cytotoxicity

resveratrol amyloind protein folding

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#1 maxwatt

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Posted 31 July 2013 - 01:32 PM


It is possible that resveratrol also inhibits the misfolding characteristic of Alzheimer's, and more significant, another effect is clearance of the toxic products of protein misfolding. Such misfolding seems ot occur in all body tissue, not the brain, and inhibiting it or clearing away the products appears a worthy target of anti-aging research.

I wonder what these resveratrol analogs are; they seem to differ in being soluble enough to achieve higher blood plasma levels than resveratrol can.

http://www.ncbi.nlm....les/PMC3145458/





Biochem Biophys Res Commun. Author manuscript; available in PMC 2012 July 15.
Published in final edited form as:


Biochem Biophys Res Commun. 2011 July 15; 410(4): 707–713.Published online 2011 May 4. doi: 10.1016/j.bbrc.2011.04.133



PMCID: PMC3145458
NIHMSID: NIHMS309870


Mechanisms of Transthyretin Cardiomyocyte Toxicity Inhibition by Resveratrol Analogs


Steve Bourgault,a,b Sungwook Choi,a,b,1 Joel N. Buxbaum,a Jeffery W. Kelly,a,b Joshua L. Price,a,b and Natàlia Reixacha,*

Author information ► Copyright and License information ►



The publisher's final edited version of this article is available at Biochem Biophys Res Commun
This article has been corrected. See the correction in volume 412 on page 196.
See other articles in PMC that cite the published article.



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Abstract


The transthyretin amyloidoses are a subset of protein misfolding diseases characterized by the extracellular deposition of aggregates derived from the plasma homotetrameric protein transthyretin (TTR2) in peripheral nerves and the heart. We have established a robust disease-relevant human cardiac tissue culture system to explore the cytotoxic effects of amyloidogenic TTR variants. We have employed this cardiac amyloidosis tissue culture model to screen 23 resveratrol analogs as inhibitors of amyloidogenic TTR-induced cytotoxicity and to investigate their mechanisms of protection. Resveratrol and its analogs kinetically stabilize the native tetramer preventing the formation of cytotoxic species. In addition, we demonstrate that resveratrol can accelerate the formation of soluble non-toxic aggregates and that the resveratrol analogs tested can bring together monomeric TTR subunits to form non-toxic native tetrameric TTR.








Also tagged with one or more of these keywords: resveratrol, amyloind, protein folding

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