Curcumin Inhibits Formation of Amyloid β Oligomers and Fibrils, Binds Plaques, and Reduces Amyloid in Vivo*

By Fusheng Yang, Giselle P. Lim, A. Begum, O. Ubeda, M. Simmons, Surendra S. Ambegaokar, Pingpin Chen, R. Kayed, C. Glabe, S. Frautschy and 1 more. Journal of Biological Chemistry, 2005

2,215 citations recorded by the source corpus.

Alzheimer's disease (AD) involves amyloid β (Aβ) accumulation, oxidative damage, and inflammation, and risk is reduced with increased antioxidant and anti-inflammatory 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 toxicity between 0.1 and 1.0 μm. Under EM, curcumin decreased dose dependently 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.

Subfields: Molecular Medicine, Neurology, Physiology

View Paper: https://www.semanticscholar.org/paper/5b0a25b8047d451067c71d7c683980d21149732a

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Citations in the corpus

Curcumin: Preventive and Therapeutic Properties in Laboratory Studies and Clinical Trials (2008, neutral): “Other studies using similar animal models have shown that curcumin effectively reduces amyloid formation, amyloid deposition, oxidative damage, and microglial activation, which have all been linked with neurodegenerative diseases (53, 285).”
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Multiple biological activities of curcumin: a short review. (2006, background): “It is suggested that dietary supplementation with curcumin may be beneficial in neurodegenerative diseases such as Alzheimer's disease (Calabrese et al., 2003; Yang et al., 2005).”
Curcumin: A review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma (2011, background): “The anti-inflammatory properties of curcumin have been investigated in a number of disease entities such as Alzheimer’s disease, cardiovascular disease, diabetes, asthma, inflammatory bowel disease, arthritis, pancreatitis and renal disease [74-90].”
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