One of the characteristic pathologies of Alzheimer disease (AD) is senile plaque, which is mainly composed of amyloid-β peptide (Aβ). Since the deposition of the aggregated Aβ is known as an initiator of the cascade of neurodegenerative events, the aggregation inhibition and the clearance of already deposited Aβ have been focused as therapeutic strategy for AD.
For the therapeutic strategy, we have developed the artificial photo-oxygenation system using photo-catalysts that selectively bind to cross-β sheet structure, which is the characteristic structure of the amyloid fibrils. These catalysts are activated by the light irradiation only when the compounds bind to the cross-β sheet structure. The activated catalysts generate the singlet oxygen, resulting in the oxygenation of the amyloid aggregates nearby the compounds. We showed that the photo-oxygenation of synthetic aggregated Aβ using these catalysts attenuated the further aggregation potency, leading to lower the neurotoxicity of Aβ in vitro. To verify the effects of the photo-oxygenation on deposited Aβ, we carried out the in vivo photo-oxygenation using AD model mice. We found that the photo-oxygenation decreased the amount of Aβ in the brain. The photo-oxygenated Aβ aggregates were cleared faster than that of non-modified Aβ aggregates in a microglia-dependent manner. These data suggest that the photo-oxygenation has a potential as novel useful strategy against AD. We would like to elucidate the molecular mechanism of the photo-oxygenation to further improve this strategy for AD therapy.