The curry spice curcumin is a potent antioxidant and has been investigated by Greg Cole's team at the University of California, Los Angeles, for possible protective roles in Alzheimer disease inflammatory processes (see ARF related news story). In a paper published online 7 December 2004 in the Journal of Biological Chemistry, Cole, first author Fusheng Yang, and colleagues point out curcumin's versatility—it busts up β-amyloid (Aβ) oligomers and plaques in vitro, protects cells, and reduces amyloid in aged mice, as well.

In their previous work, Cole and colleagues had noted not only reductions in oxidative and inflammatory markers, but also reductions in both Aβ levels and plaque burden in APPSw (Tg2576) transgenic mice fed curcumin. Given that curcumin (diferulomethane) has structural similarities to Congo red and RS-0406, both of which inhibit Aβ aggregation, the researchers explored the possibility that curcumin might have interfered with Aβ aggregation in their earlier studies. (Some of these in vitro results were presented at the 2002 meeting of the Japan Dementia Society, and published in subsequent review papers by Cole's group.)

In keeping with another recent in vitro study (Ono et al., 2004), Yang and colleagues found curcumin’s actions to be impressive, proving itself a better inhibitor of Aβ40 aggregation than fellow NSAIDs ibuprofen or naproxen. It inhibited aggregation of Aβ40 in a dose-dependent manner (IC50=0.81 μM, PMoving on to work with differentiated SH-SY5Y neuroblastoma cells challenged with Aβ42 oligomer (100 nM), Yang and colleagues found that curcumin, at a range of doses (0 - 5 μM), significantly reduced cell toxicity. "[T]his treatment effect was most effective at 0.1 and 1 μM curcumin, since the inhibitory effect appeared to plateau with 2.5 and 5 μM curcumin," the authors note.

Finally, the authors found that proof was indeed in the pudding when they extended their experiments to APPSw mice. Previously, Cole's group had shown amyloid reduction in "middle-aged" mice, fed curcumin from 10 to 16 months of age, a period of rapid amyloid accumulation in these mice. In the current study, they looked at what effect curcumin might have on animals that already have significant amyloid accumulation. Yang and colleagues found that dietary curcumin (500 ppm in chow) from 17 - 22 months of age significantly reduced plaque burden (-32.5 percent, PCurcumin seems like an opportunity too good to ignore. Beyond its antioxidant, antiinflammatory, and antiaggregation effects, there have been suggestions that curcumin could serve as a metal chelator, removing metals that might help seed or stabilize Aβ oligomers (Baum and Ng, 2004 ). From a practical perspective, the compound has advantages over other amyloid-busting compounds like Congo red and R-S106; the authors note that high doses are apparently safe in humans, and the spice is able to penetrate the blood-brain barrier effectively, thanks to its low molecular weight and polar structure. And then there's the gustatory factor. Many of us will welcome the incentive to spend more time dining on curries!—Hakon Heimer.

Reference:
Yang F, Lim GP, Begum AN, Ubeda OJ, Simmons MR, Ambegaokar SS, Chen PP, Kayed R, Glabe CG, Frautschy SA, Cole GM. Curcumin inhibits formation of Aβ oligomers and fibrils and binds plaques and reduces amyloid in vivo. J Biol Chem. 2004 Dec 7; [Epub ahead of print] Abstract

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  1. Curcumin also impacts aluminum binding to chromatin DNA, which is of relevance. After aluminum mordanting of chicken blood smears, several chelating dyes and reagents were found to detect metal binding to chromatin DNA by fluorescence microscopy. One of them [the reagents] was curcumin. Aluminum is a risk factor for AD.

    References:

    . Aluminium binding to chromatin DNA as revealed by formation of fluorescent complexes with 8-hydroxyquinoline and other ligands. J Microsc. 1989 Aug;155(Pt 2):227-30. PubMed.

References

News Citations

  1. Is It the Curry?

Paper Citations

  1. . Curcumin has potent anti-amyloidogenic effects for Alzheimer's beta-amyloid fibrils in vitro. J Neurosci Res. 2004 Mar 15;75(6):742-50. PubMed.
  2. . Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer's disease animal models. J Alzheimers Dis. 2004 Aug;6(4):367-77; discussion 443-9. PubMed.
  3. . Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem. 2005 Feb 18;280(7):5892-901. PubMed.

Further Reading

Papers

  1. . Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem. 2005 Feb 18;280(7):5892-901. PubMed.

Primary Papers

  1. . Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem. 2005 Feb 18;280(7):5892-901. PubMed.