Self-Assembly Molecular Chaperone to Concurrently Inhibit the Production and Aggregation of Amyloid β Peptide Associated with Alzheimer's Disease.

Abstract

Amyloid β peptide (Aβ) plays a crucial role in the pathogenesis of Alzheimer's disease (AD). Currently, decreasing Aβ production and preventing Aβ aggregation are thought to be important strategies in anti-AD therapy. However, inhibiting Aβ production or aggregation in isolation is not sufficient to reverse the neurodegenerative process of AD patients in clinical testing. Here, a self-assembly molecular chaperone (SAMC) consisting of γ-secretase inhibitor DAPT and mixed-shell polymeric micelles is devised, serving as a bifunctional suppressor of AD. This two-in-one combinational system can simultaneously inhibit Aβ production and aggregation, which would contribute to enhancing the therapeutic effect by decreasing Aβ levels. Decorating a neuron-specific RVG29 peptide onto the surface, the DAPT-incorporated SAMC can specifically target neuronal cells and, thus, will relieve the strong side effect of DAPT on normal cells. Therefore, this combination strategy holds great potential to open up an avenue for AD treatment.