A Supramolecular Protein Assembly Intrinsically Rescues Memory Deficits in an Alzheimer's Disease Mouse Model.

Abstract

Supramolecular protein assemblies have been used as intelligent drug delivery systems that can encapsulate drugs and transport them to specific tissues or cells. However, the known methods for designing supramolecular protein assemblies for transportation across the blood-brain barrier (BBB) remain challenging and inefficient. Herein, we report that the supramolecular recombinant-protein-based strategy enables the biosynthesis and production of a supramolecular protein assembly that is intrinsically capable of crossing the BBB. The recombinant protein constituting the essential part of apolipoprotein A1 can self-assemble into a supramolecular protein assembly known as a nanodisc. The nanodisc could efficiently enter the brain of an Alzheimer's disease mouse model, recognize Aβ_1-42, eliminate amyloid plaques, promote neurogenesis, and ameliorate cognitive impairment. This work opens a new field for supramolecular protein assemblies and offers a new avenue for designing versatile and intelligent supramolecular biomaterials.