Attenuation of the Aggregation and Neurotoxicity of Amyloid‐β Peptides by Catalytic Photooxygenation |
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| Authors: | Dr. Atsuhiko Taniguchi Dr. Daisuke Sasaki Azusa Shiohara Prof. Takeshi Iwatsubo Dr. Taisuke Tomita Dr. Youhei Sohma Prof. Motomu Kanai |
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| Affiliation: | 1. Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo‐ku, Tokyo 113‐0033 (Japan);2. Japan Science and Technology Agency (JST), ERATO, Kanai Life Science Catalysis Project, Bunkyo‐ku, Tokyo 113‐0033 (Japan);3. Graduate School of Medicine, The University of Tokyo, Bunkyo‐ku, Tokyo 113‐0033 (Japan) |
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| 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 Tyr10, His13, His14, and Met35 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. |
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| Keywords: | aggregation Alzheimer’ s disease amyloid‐beta peptides oxygenation |
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