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

Huang, F (Huang, Fan)^[ 1,2,3 ] ; Qu, AT (Qu, Aoting)^[ 1 ] ; Yang, HR (Yang, Huiru)^[ 1 ] ; Zhu, L (Zhu, Lin)^[ 1 ] ; Zhou, H (Zhou, Hao)^[ 4 ] ; Liu, JF (Liu, Jianfeng)^[ 2,3 ] ; Long, JF (Long, Jiafu)^[ 4,5 ] ; Shi, LQ (Shi, Linqi)^[ 1,5 ]

ACS MACRO LETTERS, 2018, 7(8): 983-989

DOI: 10.1021/acsmacrolett.8b00495

 WOS:000444659000016

Abstract

Amyloid beta peptide (A beta) plays a crucial role in the pathogenesis of Alzheimer's disease (AD). Currently, decreasing A beta production and preventing A beta aggregation are thought to be important strategies in anti-AD therapy. However, inhibiting A beta 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 gamma-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 A beta production and aggregation, which would contribute to enhancing the therapeutic effect by decreasing A beta 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.