Maintenance of amyloid β peptide homeostasis by artificial chaperones based on mixed-shell polymeric micelles

Angew Chem Int Ed Engl. 2014 Aug 18;53(34):8985-90. doi: 10.1002/anie.201400735. Epub 2014 Jul 1.

Abstract

The disruption of Aβ homeostasis, which results in the accumulation of neurotoxic amyloids, is the fundamental cause of Alzheimer's disease (AD). Molecular chaperones play a critical role in controlling undesired protein misfolding and maintaining intricate proteostasis in vivo. Inspired by a natural molecular chaperone, an artificial chaperone consisting of mixed-shell polymeric micelles (MSPMs) has been devised with tunable surface properties, serving as a suppressor of AD. Taking advantage of biocompatibility, selectivity toward aberrant proteins, and long blood circulation, these MSPM-based chaperones can maintain Aβ homeostasis by a combination of inhibiting Aβ fibrillation and facilitating Aβ aggregate clearance and simultaneously reducing Aβ-mediated neurotoxicity. The balance of hydrophilic/hydrophobic moieties on the surface of MSPMs is important for their enhanced therapeutic effect.

Keywords: Alzheimer’s disease; amyloid β peptide; artificial chaperones; homeostasis; polymeric micelles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / chemistry*
  • Circular Dichroism
  • Homeostasis*
  • Kinetics
  • Micelles*
  • Microscopy, Electron, Transmission
  • Molecular Chaperones / chemistry*
  • Polymers / chemistry*
  • Spectrophotometry, Ultraviolet

Substances

  • Amyloid beta-Peptides
  • Micelles
  • Molecular Chaperones
  • Polymers