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Computationally Guided Protein-Gold Nanostructures for Targeted Recognition and Cleavage of Human Amyloid-β Plaques

GSE324517 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2026/05/16 Platform GPL34290
Summary
Targeted clearance of pre-existing amyloid-β (Aβ) aggregation remains a central challenge in Alzheimer’s disease (AD) therapy. Here we report a computationally guided protein-gold hybrid nanostructure, Aβ3FTnAu, which integrates Aβ-recognition motifs into self-assembled human ferritin nanocages containing confined gold nanostructures, enabling selective engagement and disassembly of aggregated human Aβ. Structural analysis and molecular simulations reveal that the engineered nanostructure establishes multivalent interactions with fibrillar Aβ and perturbs key stabilizing interfaces, leading to progressive fibril destabilization. In 5×FAD transgenic mice, systemic administration of Aβ3FTnAu reduced cerebral amyloid burden, preserved synaptic integrity, and improved cognitive performance. This work establishes a rationally designed bioactive nanomaterial for targeted remodeling of pathological protein aggregates and highlights a generalizable strategy for engineering functional nanostructures to intervene in neurodegenerative proteinopathies.
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Also filed as BioProject PRJNA1435723 and SRA study SRP682803. Searching any of these in the dataset finder brings you back here.

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