Curcumin inhibits formation of amyloid β oligomers and fibrils, binds plaques, and reduces amyloid in vivo

Fusheng Yang, Giselle P. Lim, Aynun N. Begum, Oliver J. Ubeda, Mychica R. Simmons, Surendra S. Ambegaokar, Pingping Chen, Rakez Kayed, Charles G. Glabe, Salley A. Frautschy, Gregory M. Cole

Research output: Contribution to journalArticle

1652 Scopus citations

Abstract

Alzheimer's disease (AD) involves amyloid β (Aβ) accumulation, oxidative damage, and inflammation, and risk is reduced with increased antioxidant and antiinflammatory consumption. The phenolic yellow curry pigment curcumin has potent anti-inflammatory and antioxidant activities and can suppress oxidative damage, inflammation, cognitive deficits, and amyloid accumulation. Since the molecular structure of curcumin suggested potential Aβ binding, we investigated whether its efficacy in AD models could be explained by effects on Aβ aggregation. Under aggregating conditions in vitro, curcumin inhibited aggregation (IC50 = 0.8 μM) as well as disaggregated fibrillar Aβ40 (IC50 = 1 μM), indicating favorable stoichiometry for inhibition. Curcumin was a better Aβ40 aggregation inhibitor than ibuprofen and naproxen, and prevented Aβ42 oligomer formation and tosicity between 0.1 and 1.0 μM. Under EM, curcumin decreased dose dependency Aβ fibril formation beginning with 0.125 μM. The effects of curcumin did not depend on Aβ sequence but on fibril-related conformation. AD and Tg2576 mice brain sections incubated with curcumin revealed preferential labeling of amyloid plaques. In vivo studies showed that curcumin injected peripherally into aged Tg mice crossed the blood-brain barrier and bound plaques. When fed to aged Tg2576 mice with advanced amyloid accumulation, curcumin labeled plaques and reduced amyloid levels and plaque burden. Hence, curcumin directly binds small β-amyloid species to block aggregation and fibril formation in vitro and in vivo. These data suggest that low dose curcumin effectively disaggregates Aβ as well as prevents fibril and oligomer formation, supporting the rationale for curcumin use in clinical trials preventing or treating AD.

Original languageEnglish (US)
Pages (from-to)5892-5901
Number of pages10
JournalJournal of Biological Chemistry
Volume280
Issue number7
DOIs
StatePublished - Feb 18 2005
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Yang, F., Lim, G. P., Begum, A. N., Ubeda, O. J., Simmons, M. R., Ambegaokar, S. S., Chen, P., Kayed, R., Glabe, C. G., Frautschy, S. A., & Cole, G. M. (2005). Curcumin inhibits formation of amyloid β oligomers and fibrils, binds plaques, and reduces amyloid in vivo. Journal of Biological Chemistry, 280(7), 5892-5901. https://doi.org/10.1074/jbc.M404751200