Attenuation of the Aggregation and Neurotoxicity of Amyloid-β Peptides by Catalytic Photooxygenation

Alzheimer's disease (AD), a progressive severe neurodegenerative disorder, is currently incurable, despite intensive efforts worldwide. Herein, we demonstrate that catalytic oxygenation of amyloid-beta peptides (A beta) might be an effective approach to treat AD. A beta 1-42 was oxygenated under physiologically-relevant conditions (pH 7.4, 37 degrees 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 A beta 1-42 exhibited considerably lower aggregation potency and neurotoxicity compared with native A beta. Photooxygenation of A beta can be performed even in the presence of cells, by using a selective flavin catalyst attached to an A beta-binding peptide; the A beta cytotoxicity was attenuated in this case as well. Furthermore, oxygenated A beta 1-42 inhibited the aggregation and cytotoxicity of native A beta.