Attenuation of the aggregation and neurotoxicity of amyloid-β peptides by catalytic photooxygenation

Angew Chem Int Ed Engl. 2014 Jan 27;53(5):1382-5. doi: 10.1002/anie.201308001. Epub 2013 Dec 11.

Abstract

Alzheimer's disease (AD), a progressive severe neurodegenerative disorder, is currently incurable, despite intensive efforts worldwide. Herein, we demonstrate that catalytic oxygenation of amyloid-β peptides (Aβ) might be an effective approach to treat AD. Aβ1-42 was oxygenated under physiologically-relevant conditions (pH 7.4, 37 °C) using a riboflavin catalyst and visible light irradiation, with modifications at the Tyr(10) , His(13) , His(14) , and Met(35) residues. The oxygenated Aβ1-42 exhibited considerably lower aggregation potency and neurotoxicity compared with native Aβ. Photooxygenation of Aβ can be performed even in the presence of cells, by using a selective flavin catalyst attached to an Aβ-binding peptide; the Aβ cytotoxicity was attenuated in this case as well. Furthermore, oxygenated Aβ1-42 inhibited the aggregation and cytotoxicity of native Aβ.

Keywords: Alzheimer’s disease; aggregation; amyloid-beta peptides; oxygenation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amyloid beta-Peptides / chemistry*
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Peptides / toxicity
  • Animals
  • Catalysis
  • Cell Survival / drug effects
  • Cells, Cultured
  • Humans
  • Light*
  • Molecular Sequence Data
  • Oxygen / chemistry*
  • PC12 Cells
  • Peptide Fragments / chemistry*
  • Peptide Fragments / metabolism
  • Peptide Fragments / toxicity
  • Rats
  • Riboflavin / chemistry

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • Oxygen
  • Riboflavin