Au23（CR）14 nanocluster restores fibril Aβ's unfolded state with abolished cytotoxicity and dissolves endogenous Aβplaques
Au23（CR）14 nanocluster restores fibril Aβ’s unfolded state with abolished cytotoxicity and dissolves endogenous Aβplaques作者机构：State Key Laboratory of Advanced Technology for Materials Synthesis and Processing Wuhan University of Technology School of Chemistry Chemical Engineering and Life Science Wuhan University of Technology
出 版 物：《National Science Review》 (国家科学评论(英文版))
年 卷 期：2020年第7卷第4期
页 面：763-774页
核心收录：
学科分类：1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 07[理学] 070205[理学-凝聚态物理] 08[工学] 080501[工学-材料物理与化学] 0805[工学-材料科学与工程（可授工学、理学学位）] 100203[医学-老年医学] 10[医学] 0702[理学-物理学]
基 金：supported by the National Natural Science Foundation of China (21975191 21805218 51873168 81803515 51533007 and 51521001) the Natural Science Foundation of Hubei Province (2018CFA002 and 2018CFB348) Wuhan University of Technology fund for first-class university first-class discipline construction projects (472-20162008) Fundamental Research Funds for the Central Universities (WUT 2018III023) Excellent Dissertation Cultivation Funds of Wuhan University of Technology (2017-YS-010)
主 题：gold nanoclusters Alzheimer’s disease restores fibril Aβ’s unfolded state abolished cytotoxicity dissolves endogenous Aβ plaques
摘 要：The misfolding of amyloid-β（Aβ） peptides from the natural unfolded state to β-sheet structure is a critical step, leading to abnormal fibrillation and formation of endogenous Aβ plaques in Alzheimer s disease（AD）. Previous studies have reported inhibition of Aβ fibrillation or disassembly of exogenous Aβ fibrils in vitro. However, soluble Aβ oligomers have been reported with increased cytotoxicity; this might partly explain why current clinical trials targeting disassembly of Aβ fibrils by anti-Aβ antibodies have failed so *** we show that Au23（CR）14(a new Au nanocluster modified by Cys-Arg（CR） dipeptide) is able to completely dissolve exogenous mature Aβ fibrils into monomers and restore the natural unfolded state of Aβ peptides from misfolded β-sheets. Furthermore, the cytotoxicity of Aβ40fibrils when dissolved by Au23（CR）14is fully abolished. More importantly, Au23（CR）14is able to completely dissolve endogenous Aβ plaques in brain slices from transgenic AD model mice. In addition, Au23（CR）14has good biocompatibility and infiltration ability across the blood–brain barrier. Taken together, this work presents a promising therapeutics candidate for AD treatment, and manifests the potential of nanotechnological approaches in the development of nanomedicines.
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