title: How curcumin affords effective protection against amyloid fibrillation in insulin.
abstract: Since the formation of amyloid structures from proteins was recognized in numerous diseases, many efforts have been devoted to the task of finding effective anti-amyloidogenic compounds. In a number of these investigations, the existence of "generic" compounds is implicitly acknowledged. Curcumin seems to be one of these compounds, possessing key structural components effective toward fibrillation prevention, and its anti-amyloidogenic property has been reported for a number of model and disease-related proteins such as lysozyme and alpha-synuclein. In this study, insulin amyloid formation has been shown to be effectively influenced by micromolar concentrations of curcumin. Under amyloidogenic conditions (pH 2.5 and 37 °C), the compound was observed to inhibit fibril formation of insulin in a dose-dependent manner. Moreover, addition of curcumin to the protein incubated under such conditions at different time points resulted in reduced amounts of final fibrils. Disaggregation of pre-formed fibrils was also observed upon addition of curcumin, as well as reduction in final fibril amounts after seeding. Overall, this compound appears to be able to interact with native, intermediate and fibrillar forms. Docking experiments suggest a potential interacting site with the B-chain of insulin, as well as the possibility for beta-sheet breaker activity.
authors.affiliation: Institute of Biochemistry and Biophysics, University of Tehran, P.O. Box 13145-1384, Tehran, Iran.
authors.forename: Atefeh
authors.initials: A
authors.lastname: Rabiee
authors.forename: Azadeh
authors.initials: A
authors.lastname: Ebrahim-Habibi
authors.forename: Atiyeh
authors.initials: A
authors.lastname: Ghasemi
authors.forename: Mohsen
authors.initials: M
authors.lastname: Nemat-Gorgani
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D003474:Curcumin / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000737:chemistry*; D007700:Kinetics; D062105:Molecular Docking Simulation; D020011:Protective Agents / Q000737:chemistry*; D013696:Temperature
chemical_list: D000682:Amyloid; D007328:Insulin; D020011:Protective Agents; D003474:Curcumin