Maintenance of Amyloid β Peptide Homeostasis by Artificial Chaperones Based on Mixed-Shell Polymeric Micelles

Authors

  • Fan Huang,

    1. Key Laboratory of Functional Polymer Materials, Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Institute of Polymer Chemistry, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, (P.R. China), Institution
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  • Jianzu Wang,

    1. Key Laboratory of Functional Polymer Materials, Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Institute of Polymer Chemistry, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, (P.R. China), Institution
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  • Aoting Qu,

    1. Key Laboratory of Functional Polymer Materials, Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Institute of Polymer Chemistry, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, (P.R. China), Institution
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  • Liangliang Shen,

    1. Key Laboratory of Functional Polymer Materials, Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Institute of Polymer Chemistry, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, (P.R. China), Institution
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  • Dr. Jinjian Liu,

    1. Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, (P.R. China)
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  • Jianfeng Liu,

    1. Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, (P.R. China)
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  • Dr. Zhenkun Zhang,

    1. Key Laboratory of Functional Polymer Materials, Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Institute of Polymer Chemistry, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, (P.R. China), Institution
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  • Yingli An,

    1. Key Laboratory of Functional Polymer Materials, Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Institute of Polymer Chemistry, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, (P.R. China), Institution
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  • Prof. Linqi Shi

    Corresponding author
    1. Key Laboratory of Functional Polymer Materials, Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Institute of Polymer Chemistry, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, (P.R. China), Institution
    • Key Laboratory of Functional Polymer Materials, Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Institute of Polymer Chemistry, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, (P.R. China), Institution

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  • This work was financially supported by the National Natural Science Foundation of China (Nos. 91127045, 51390483, 21274067, 81171371, 51203189), the National Basic Research Program of China (973 Program, No. 2011CB932503), and PCSIRT (IRT1257).

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.

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