Photo-oxygenation inhibits tau amyloid formation

Summary

Alzheimer’s Disease (AD) is a neurodegenerative disease, whose patients are dramatically increasing in the world. However, there is no cure and prevention strategies for AD yet. AD is characterized by two types of depositions of amyloid proteins, amyloid β peptide and tau with cross-β-sheet structure. For AD therapy, it is important to suppress the formation and the spread of these amyloid depositions. Previously, we have reported photo-oxygenation catalyst which could selectively oxygenate amyloid proteins under light irradiation via binding to cross-β-sheet structure and photo-oxygenation could suppress the aggregation and the toxicity of amyloid β peptide (Taniguchi et al., Nat Chem 2016; Ni et al., Chem 2018). However, the effect of photo-oxygenation on tau amyloid remains unclear.
In this study, we developed the new catalyst which oxygenates the tau amyloid more effectively than previous catalysts. Photo-oxygenation markedly suppressed the tau aggregation, via the inhibition of tau seeding activity in vitro and in cultured cells. Several lines of evidence suggest that the seeding activity of tau amyloid is prerequisite for tau pathology spreading, which is correlated with neuronal dysfunction and neurodegeneration in the brains of AD patients. Therefore, our results suggested that photo-oxygenation for tau amyloid has the potential for AD therapy by attenuating the seeding activity.

 

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