Heat Shock Protein Inspired Nanochaperones Restore Amyloid-? Homeostasis for Preventative Therapy of Alzheimer's Disease.

ABSTRACT: Amyloid beta (A?) aggregation is generally believed as the crucial and primary cause of Alzheimer's disease (AD). However, current A?-targeted therapeutic strategies show limited disease-modifying efficacy due to the irreversible damages in the late stage of AD, thus the treatment should be given before the formation of deposition and target primary A? species rather than advanced plaques. Herein, inspired by heat shock protein, a self-assembly nanochaperone based on mixed-shell polymeric micelle (MSPM) is devised to act as a novel strategy for AD prevention. With unique surface hydrophobic domains, this nanochaperone can selectively capture A? peptides, effectively suppress A? aggregation, and remarkably reduce A?-mediated cytotoxicity. Moreover, the formed nanochaperone-A? complex after A? adsorption can be easily phagocytosed by microglia and thereby facilitates A? clearance. As a result, the nanochaperone reduces A? burden, attenuates A?-induced inflammation, and eventually rescues the cognitive deficits of APP/PS1 transgenic AD mice. These results indicate that this biomimetic nanochaperone can successfully prevent the onset of AD symptoms and serve as a promising candidate for prophylactic treatment of AD.

SUBMITTER: Yang H 

PROVIDER: S-EPMC6864524 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature