Photo-oxygenation by a biocompatible catalyst reduces amyloid-β levels in Alzheimer's disease mice
| Autor: | Reiko Koike, Taisuke Tomita, Yusuke Shimizu, Takanobu Suzuki, Motomu Kanai, Yung Wen Chiu, Sho Takatori, Yukiko Hori, Wenbo Wang, Shuta Ozawa, Tohru Fukuyama, Atsuhiko Taniguchi, Youhei Sohma, Satoshi Yokoshima |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Boron Compounds Amyloid Cellular respiration medicine.medical_treatment Peptide 03 medical and health sciences Mice Protein Aggregates 0302 clinical medicine In vivo Alzheimer Disease mental disorders medicine Animals Humans chemistry.chemical_classification Amyloid beta-Peptides Microglia biology Neurotoxicity Brain Immunotherapy Phototherapy medicine.disease Disease Models Animal 030104 developmental biology medicine.anatomical_structure chemistry Cancer research biology.protein Neurology (clinical) Antibody 030217 neurology & neurosurgery |
| Zdroj: | Brain : a journal of neurology. 144(6) |
| ISSN: | 1460-2156 |
| Popis: | Amyloid formation and the deposition of the amyloid-β peptide are hallmarks of Alzheimer’s disease pathogenesis. Immunotherapies using anti-amyloid-β antibodies have been highlighted as a promising approach for the prevention and treatment of Alzheimer’s disease by enhancing microglial clearance of amyloid-β peptide. However, the efficiency of antibody delivery into the brain is limited, and therefore an alternative strategy to facilitate the clearance of brain amyloid is needed. We previously developed an artificial photo-oxygenation system using a low molecular weight catalytic compound. The photocatalyst specifically attached oxygen atoms to amyloids upon irradiation with light, and successfully reduced the neurotoxicity of aggregated amyloid-β via inhibition of amyloid formation. However, the therapeutic effect and mode of actions of the photo-oxygenation system in vivo remained unclear. In this study, we demonstrate that photo-oxygenation facilitates the clearance of aggregated amyloid-β from the brains of living Alzheimer’s disease model mice, and enhances the microglial degradation of amyloid-β peptide. These results suggest that photo-oxygenation may represent a novel anti-amyloid-β strategy in Alzheimer’s disease, which is compatible with immunotherapy. |
| Databáze: | OpenAIRE |
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