Polyphenol-induced dissociation of various amyloid fibrils results in a methionine-independent formation of ROS

Hila Shoval, Lev Weiner, Ehud Gazit, Michal Levy, Ilya Pinchuk, Dov Lichtenberg

Research output: Contribution to journalArticlepeer-review

Abstract

Fibrillization of amyloid polypeptides is accompanied by formation of reactive oxygen species (ROS), which, in turn, is assumed to further promote amyloid-related pathologies. Different polyphenols, all of which are established antioxidants, cause dissociation of amyloid fibrils. This study addresses the latter, poorly understood process. Specifically, we have investigated the dissociation of Aβ42 fibrils by six different polyphenols, using electron microscopy and spectrofluorometric analysis. Simultanously, we have monitored the production of ROS using electron spin resonance (ESR) and the commercially available peroxide assay kit. Using the same methods we found that curcumin, one of the most potent destabilizing agents of Aβ42, induced dissociation of fibrils of other amyloid polypeptides [Aβ40, Aβ42Nle35, islet amyloid polypeptide and a fragment of α-synuclein]. When the solution contained traces of transition metal, all the dissociation reactions were accompanied by ROS formation, independent of the presence of a methionine residue. Kinetic studies show that the formation of ROS lags behind dissociation, indicating that if casual relationship exists between these two processes, then ROS formation may be considered a consequence and not a cause of dissociation. These findings open new avenues in amyloid research that will be required to gain further understanding of our results and of their implications.

Original languageEnglish
Pages (from-to)1570-1577
Number of pages8
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1784
Issue number11
DOIs
StatePublished - Nov 2008

Keywords

  • Amyloid disease
  • Electron spin resonance
  • Fibril dissociation
  • Free radicals
  • Polyphenols
  • Self-Assembly

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