title: Curcumin modulates the self-assembly of the islet amyloid polypeptide by disassembling α-helix.
abstract: Understanding how small molecules affect amyloid formation is of major biomedical and pharmaceutical importance due to the association of amyloid with incurable diseases including Alzheimer's, Parkinson's, and type II diabetes. Using solution state (1)H NMR, we demonstrate that curcumin, a planar biphenolic compound found in the Indian spice turmeric, delays the self-assembly of islet amyloid polypeptide to NMR-invisible assemblies. Accompanying circular dichroism studies show that curcumin disassembles α-helix in maturing assemblies of IAPP. The amount of α-helix disassembled correlates with predicted and experimentally determined helical content of IAPP obtained by others. Taken together, these results indicate that curcumin modulates IAPP self-assembly by unfolding α-helix on pathway to amyloid. The implications of this work in the elucidation of the mechanism for amyloid formation by IAPP in the presence of curcumin are discussed.
authors.affiliation: Carlson School of Chemistry and Biochemistry, Clark University, 950 Main Street, Worcester, MA 01610, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Sparks
authors.forename: Gai
authors.initials: G
authors.lastname: Liu
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Robbins
authors.forename: Noel D
authors.initials: ND
authors.lastname: Lazo
mesh_terms: D000595:Amino Acid Sequence; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D004396:Coloring Agents / Q000737:chemistry / Q000494:pharmacology*; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000737:chemistry*; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary / Q000187:drug effects; D058767:Protein Unfolding
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004396:Coloring Agents; D058228:Islet Amyloid Polypeptide; D003474:Curcumin