Self-triggered click reaction in an Alzheimer's disease model: in situ bifunctional drug synthesis catalyzed by neurotoxic copper accumulated in amyloid-β plaques

摘要: Cu is one of the essential elements for life. Its dyshomeostasis has been demonstrated to be closely related neurodegenerative disorders, such as Alzheimer's disease (AD), which characterized by amyloid-β (Aβ) aggregation and accumulation. It a great challenge how take advantage neurotoxic fight make it helpful. Herein, we report that accumulated in Aβ plaques can effectively catalyze an azide–alkyne bioorthogonal cycloaddition reaction fluorophore activation drug synthesis living cells, transgenic AD model Caenorhabditis elegans CL2006, brain slices triple mice. More importantly, situ synthesized bifunctional 6 disassemble Aβ–Cu aggregates extracting photo-oxygenating synergistically, suppressing Aβ-mediated paralysis diminishing locomotion defects CL2006 strain. Our results demonstrate taking ions plaque click achieve both self-triggered self-regulated therapy. To best our knowledge, catalyzed local physiological environment not reported. This work may open up new avenue multifunctional using endogenous metal treatment diseases.