RRC ID 64351
Author Ozawa S, Hori Y, Shimizu Y, Taniguchi A, Suzuki T, Wang W, Chiu YW, Koike R, Yokoshima S, Fukuyama T, Takatori S, Sohma Y, Kanai M, Tomita T.
Title Photo-oxygenation by a biocompatible catalyst reduces amyloid-β levels in Alzheimer's disease mice.
Journal Brain
Abstract 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.
Volume 144(6)
Pages 1884-1897
Published 2021-7-28
DOI 10.1093/brain/awab058
PII 6224831
PMID 33851209
MeSH Alzheimer Disease / pathology* Amyloid beta-Peptides / drug effects* Amyloid beta-Peptides / metabolism* Animals Boron Compounds / pharmacology* Brain / drug effects* Brain / pathology Disease Models, Animal Humans Mice Microglia / metabolism Phototherapy / methods Protein Aggregates / drug effects
IF 11.337
Human and Animal Cells MG6(RCB2403)