Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer's disease animal models

Curcumin is a polyphenolic diketone from turmeric. Because of its anti-oxidant and anti-inflammatory effects, it was tested in animal models of Alzheimer's disease, reducing levels of amyloid and oxidized proteins and preventing cognitive deficits. An alternative mechanism of these effects is metal chelation, which may reduce amyloid aggregation or oxidative neurotoxicity. Metals call induce Abeta aggregation and toxicity, and are concentrated in AD brain. Chelators desferrioxamine and clioquinol have exhibited anti-AD effects. Using spectrophotometry, we quantified curcumin affinity for copper, zinc, and iron ions. Zn2+ showed little binding, but each Cu2+ or Fe2+ ion appeared to bind at least two curcumin molecules. The interaction of curcumin with copper reached half-maximum at similar to3-12 muM copper and exhibited positive cooperativity, with K(d1)similar to10-60 muM and K(d2)similar to1.3 muM (for binding of the first and second curcumin molecules, respectively). Curcumin-iron interaction reached half-maximum at similar to2.5-5 muM iron and exhibited negative cooperativity, with K(d1)similar to0.5-1.6 muM and K(d2)similar to50-100 muM. Curcumin and its metabolites can attain these levels in vivo, suggesting physiological relevance. Since curcumin more readily binds the redox-active metals iron and copper than redox-mactive zinc, curcumin might exert a net protective effect against Abeta toxicity or might suppress inflammatory damage by preventing metal induction of NF-kappaB.